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 CODE
Project Coincidence detection of proteins and lipids in regulation of cellular membrane dynamics
Researcher (PI) Harald STENMARK
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Advanced Grant (AdG), LS3, ERC-2017-ADG
Summary Specific recruitment of different proteins to distinct intracellular membranes is fundamental in the biology of eukaryotic cells, but the molecular basis for specificity is incompletely understood. This proposal investigates the hypothesis that coincidence detection of proteins and lipids constitutes a major mechanism for specific recruitment of proteins to intracellular membranes in order to control cellular membrane dynamics. CODE will establish and validate mathematical models for coincidence detection, identify and functionally characterise novel coincidence detectors, and engineer artificial coincidence detectors as novel tools in cell biology and biotechnology.
Summary
Specific recruitment of different proteins to distinct intracellular membranes is fundamental in the biology of eukaryotic cells, but the molecular basis for specificity is incompletely understood. This proposal investigates the hypothesis that coincidence detection of proteins and lipids constitutes a major mechanism for specific recruitment of proteins to intracellular membranes in order to control cellular membrane dynamics. CODE will establish and validate mathematical models for coincidence detection, identify and functionally characterise novel coincidence detectors, and engineer artificial coincidence detectors as novel tools in cell biology and biotechnology.
Max ERC Funding
2 500 000 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym EPIFISH
Project INNOVATIVE EPIGENETIC MARKERS FOR FISH DOMESTICATION
Researcher (PI) Jorge Manuel De Oliveira Fernandes
Host Institution (HI) NORD UNIVERSITET
Call Details Consolidator Grant (CoG), LS9, ERC-2015-CoG
Summary Aquaculture is the fastest growing food production sector in the world, since there is an increasing demand for fish protein to feed a growing global population, which cannot be met by fisheries. In order to ensure the sustainability of this sector it is critical to domesticate and selectively improve the major commercial fish species. To date, the genetic markers used in selective breeding of fish account only for a fraction of the observed phenotypic variation. EPIFISH is a scientifically innovative and timely project that will address fish domestication and selection from a new perspective using a multidisciplinary approach. The rapid pace of substantial phenotypic changes during adaptation to new environmental conditions in fish undergoing domestication raises the original hypothesis that epigenetic mechanisms are involved in this process. Thus, the overarching aim of EPIFISH is to ascertain the importance of epigenetics in fish domestication using the Nile tilapia (Oreochromis niloticus) as model species. Specific objectives are i) to determine how selection affects the miRNA transcriptome and the epigenetic landscape during domestication, ii) to perform a functional characterization of miRNA variants and epigenetic alleles associated with growth, and iii) to validate them as potential epigenetic markers for future selective breeding programmes. The identification of epigenetic markers will be a ground-breaking element of EPIFISH with major impact on aquaculture biotechnology, since they will enable the development and application of epigenomic selection as a new feature in future selective breeding programmes. Moreover, the project outcomes will provide novel mechanistic insights into the role of epigenetics in fish domestication, which will surely open new horizons for future frontier research in epigenetics, namely transgenerational inheritance and nutritional epigenetics.
Summary
Aquaculture is the fastest growing food production sector in the world, since there is an increasing demand for fish protein to feed a growing global population, which cannot be met by fisheries. In order to ensure the sustainability of this sector it is critical to domesticate and selectively improve the major commercial fish species. To date, the genetic markers used in selective breeding of fish account only for a fraction of the observed phenotypic variation. EPIFISH is a scientifically innovative and timely project that will address fish domestication and selection from a new perspective using a multidisciplinary approach. The rapid pace of substantial phenotypic changes during adaptation to new environmental conditions in fish undergoing domestication raises the original hypothesis that epigenetic mechanisms are involved in this process. Thus, the overarching aim of EPIFISH is to ascertain the importance of epigenetics in fish domestication using the Nile tilapia (Oreochromis niloticus) as model species. Specific objectives are i) to determine how selection affects the miRNA transcriptome and the epigenetic landscape during domestication, ii) to perform a functional characterization of miRNA variants and epigenetic alleles associated with growth, and iii) to validate them as potential epigenetic markers for future selective breeding programmes. The identification of epigenetic markers will be a ground-breaking element of EPIFISH with major impact on aquaculture biotechnology, since they will enable the development and application of epigenomic selection as a new feature in future selective breeding programmes. Moreover, the project outcomes will provide novel mechanistic insights into the role of epigenetics in fish domestication, which will surely open new horizons for future frontier research in epigenetics, namely transgenerational inheritance and nutritional epigenetics.
Max ERC Funding
1 996 189 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym ImPRESS
Project Imaging Perfusion Restrictions from Extracellular Solid Stress
Researcher (PI) Kyrre Eeg Emblem
Host Institution (HI) OSLO UNIVERSITETSSYKEHUS HF
Call Details Starting Grant (StG), LS7, ERC-2017-STG
Summary Even the perfect cancer drug must reach its target to have an effect. The ImPRESS project main objective is to develop a novel imaging paradigm coined Restricted Perfusion Imaging (RPI) to reveal - for the first time in humans - vascular restrictions in solid cancers caused by mechanical solid stress, and use RPI to demonstrate that alleviating this force will repair the cancerous microenvironment and improve therapeutic response. Delivery of anti-cancer drugs to the tumor is critically dependent on a functional vascular bed. Developing biomarkers that can measure how mechanical forces in a solid tumor impair perfusion and promotes therapy resistance is essential for treatment of disease.
The ImPRESS project is based on the following observations; (I) pre-clinical work suggests that therapies targeting the tumor microenvironment and extracellular matrix may enhance drug delivery by decompressing tumor vessels; (II) results from animal models may not be transferable because compressive forces in human tumors in vivo can be many times higher; and (III) there are no available imaging technologies for medical diagnostics of solid stress in human cancers. Using RPI, ImPRESS will conduct a comprehensive series of innovative studies in brain cancer patients to answer three key questions: (Q1) Can we image vascular restrictions in human cancers and map how the vasculature changes with tumor growth or treatment? (Q2) Can we use medical engineering to image solid stress in vivo? (Q3) Can RPI show that matrix-depleting drugs improve patient response to conventional chemo- and radiation therapy as well as new targeted therapies?
The ImPRESS project holds a unique position to answer these questions by our unrivaled experience with advanced imaging of cancer patients. With successful delivery, ImPRESS will have a direct impact on patient treatment and establish an imaging paradigm that will pave the way for new scientific knowledge on how to revitalize cancer therapies.
Summary
Even the perfect cancer drug must reach its target to have an effect. The ImPRESS project main objective is to develop a novel imaging paradigm coined Restricted Perfusion Imaging (RPI) to reveal - for the first time in humans - vascular restrictions in solid cancers caused by mechanical solid stress, and use RPI to demonstrate that alleviating this force will repair the cancerous microenvironment and improve therapeutic response. Delivery of anti-cancer drugs to the tumor is critically dependent on a functional vascular bed. Developing biomarkers that can measure how mechanical forces in a solid tumor impair perfusion and promotes therapy resistance is essential for treatment of disease.
The ImPRESS project is based on the following observations; (I) pre-clinical work suggests that therapies targeting the tumor microenvironment and extracellular matrix may enhance drug delivery by decompressing tumor vessels; (II) results from animal models may not be transferable because compressive forces in human tumors in vivo can be many times higher; and (III) there are no available imaging technologies for medical diagnostics of solid stress in human cancers. Using RPI, ImPRESS will conduct a comprehensive series of innovative studies in brain cancer patients to answer three key questions: (Q1) Can we image vascular restrictions in human cancers and map how the vasculature changes with tumor growth or treatment? (Q2) Can we use medical engineering to image solid stress in vivo? (Q3) Can RPI show that matrix-depleting drugs improve patient response to conventional chemo- and radiation therapy as well as new targeted therapies?
The ImPRESS project holds a unique position to answer these questions by our unrivaled experience with advanced imaging of cancer patients. With successful delivery, ImPRESS will have a direct impact on patient treatment and establish an imaging paradigm that will pave the way for new scientific knowledge on how to revitalize cancer therapies.
Max ERC Funding
1 499 638 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym macroevolution.abc
Project Abiota, Biota, Constraints in Macroevolutionary Processes
Researcher (PI) Lee Hsiang Liow
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Consolidator Grant (CoG), LS8, ERC-2016-COG
Summary To what degree do microevolutionary processes that happen on a generational time scale matter for macroevolutionary patterns recorded on time scales of millions of years in the fossil record? To answer this fundamental question in evolutionary biology, we need a model system in which we can overcome the conceptual and empirical boundaries imposed by disparate timescales. macroevolution.abc will develop bryozoans as the Drosophila of macroevolution, integrating molecular, fossil, phenotypic, ecological and environmental data to shed light on the currently inaccessible “Dark Time Scale” (thousands, to tens of thousands of years), spanning the chasm between microevolution studied by population geneticists and evolutionary ecologists and macroevolution studied by paleontologists and comparative phylogeneticists. Using bryozoans, a little-known but uniquely ideal study group for evolutionary questions, I will generate, then cross-integrate, (i) empirical time series of intra- and interspecific biotic interactions; (ii) phenotypic data describing variation within genetic individuals, variation among contemporaneous individuals in both extinct and living populations; (iii) robust estimates of abundance shifts in fossil populations; and (iv) speciation and extinction rate estimates from molecular phylogenies and the fossil record. The new bryozoan model evolutionary system will provide answers to previously intractable questions such as “do ecological interactions crucial for individual survival matter for group diversification patterns observed on geological time scales” and “why do we have to wait a million years for bursts of phenotypic change”?
Summary
To what degree do microevolutionary processes that happen on a generational time scale matter for macroevolutionary patterns recorded on time scales of millions of years in the fossil record? To answer this fundamental question in evolutionary biology, we need a model system in which we can overcome the conceptual and empirical boundaries imposed by disparate timescales. macroevolution.abc will develop bryozoans as the Drosophila of macroevolution, integrating molecular, fossil, phenotypic, ecological and environmental data to shed light on the currently inaccessible “Dark Time Scale” (thousands, to tens of thousands of years), spanning the chasm between microevolution studied by population geneticists and evolutionary ecologists and macroevolution studied by paleontologists and comparative phylogeneticists. Using bryozoans, a little-known but uniquely ideal study group for evolutionary questions, I will generate, then cross-integrate, (i) empirical time series of intra- and interspecific biotic interactions; (ii) phenotypic data describing variation within genetic individuals, variation among contemporaneous individuals in both extinct and living populations; (iii) robust estimates of abundance shifts in fossil populations; and (iv) speciation and extinction rate estimates from molecular phylogenies and the fossil record. The new bryozoan model evolutionary system will provide answers to previously intractable questions such as “do ecological interactions crucial for individual survival matter for group diversification patterns observed on geological time scales” and “why do we have to wait a million years for bursts of phenotypic change”?
Max ERC Funding
1 990 213 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym NterAct
Project Discovery and functional significance of post-translational N-terminal acetylation
Researcher (PI) Thomas ARNESEN
Host Institution (HI) UNIVERSITETET I BERGEN
Call Details Consolidator Grant (CoG), LS1, ERC-2017-COG
Summary In mammalian cells, N-terminal (Nt) acetylation is one of the most abundant protein modifications. It is catalysed by N-terminal acetyltransferases (NATs) and mostly occurs co-translationally. However, in contrast to the defined co-translational NATs, post-translational NATs which have crucial regulatory roles are mostly unexplored. Distinct peptide hormones regulate appetite, metabolism, sexual behaviour and pain, and their biological activity is critically modulated by post-translational Nt-acetylation. However, the identity of the NAT responsible for this modification, ‘HormNat’, is unknown, thus the molecular and physiological ramifications of this regulatory circuit remain elusive. Another example is actin, a key regulator of cell motility and cell division. The actin N-terminus is crucial for actin function and in mammals actin is modified by an unknown post-translational NAT, ‘ActNat’. Hence, the objectives of this project are to identify these human NATs acting post-translationally, and to investigate their molecular mechanisms, regulation and impact.
We will identify the novel NATs by a combination of classical and newly developed in-house tools like in vitro acetylation assays, unique bisubstrate analogues, Nt-acetylation specific antibodies, and targeted mass spectrometry. Interestingly, Nt-acetylation is considered irreversible, but there is reason to believe that specific substrates are Nt-deacetylated. Elucidation of post-translational NATs and the reversible nature of Nt-acetylation would represent a new era in the field of protein and peptide regulation and identify key cellular and organismal switches.
Summary
In mammalian cells, N-terminal (Nt) acetylation is one of the most abundant protein modifications. It is catalysed by N-terminal acetyltransferases (NATs) and mostly occurs co-translationally. However, in contrast to the defined co-translational NATs, post-translational NATs which have crucial regulatory roles are mostly unexplored. Distinct peptide hormones regulate appetite, metabolism, sexual behaviour and pain, and their biological activity is critically modulated by post-translational Nt-acetylation. However, the identity of the NAT responsible for this modification, ‘HormNat’, is unknown, thus the molecular and physiological ramifications of this regulatory circuit remain elusive. Another example is actin, a key regulator of cell motility and cell division. The actin N-terminus is crucial for actin function and in mammals actin is modified by an unknown post-translational NAT, ‘ActNat’. Hence, the objectives of this project are to identify these human NATs acting post-translationally, and to investigate their molecular mechanisms, regulation and impact.
We will identify the novel NATs by a combination of classical and newly developed in-house tools like in vitro acetylation assays, unique bisubstrate analogues, Nt-acetylation specific antibodies, and targeted mass spectrometry. Interestingly, Nt-acetylation is considered irreversible, but there is reason to believe that specific substrates are Nt-deacetylated. Elucidation of post-translational NATs and the reversible nature of Nt-acetylation would represent a new era in the field of protein and peptide regulation and identify key cellular and organismal switches.
Max ERC Funding
1 999 273 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
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 ProstOmics
Project 'Tissue is the issue': a multi-omics approach to improve prostate cancer diagnosis
Researcher (PI) May-Britt Tessem
Host Institution (HI) NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU
Call Details Starting Grant (StG), LS7, ERC-2017-STG
Summary Overtreatment in prostate cancer (PCa) is a burden for health care economy and for quality of life. Correct diagnosis of early stage PCa is challenging given the limitations of the currently available clinical tools and the biological understanding of PCa. In this inter-disciplinary project, I propose an innovative approach enabling several cutting-edge ‘omics’ technologies (spatial metabolomics, genomics, transcriptomics) as well as histopathology to be performed on the same tissue sample. My goal is to reveal the molecular mechanisms of novel, but also promising metabolite biomarkers (citrate, polyamines, succinate and zinc) and their connection to recurrence, tissue heterogeneity and immune responses in complex human tissues. Such markers can personalize PCa diagnosis, open up new treatment strategies and fundamentally change the view of how to analyze tissue samples in the future. Furthermore, I want to demonstrate that citrate and polyamines are reliable prognostic markers that can be analyzed both in tissue and in patients in vivo by MR spectroscopic imaging. This work is made possible by the availability of high-quality fresh frozen tissue biobanks of prostatectomy biopsies with 5-10 years of follow-up data (N=1000)/slices (N=1000) and targeted in vivo snap-shot biopsies from clinical MR guided procedures (N=100). Among other techniques, I will implement high speed MALDI imaging (RapifleX MALDI TissueTyper) to the multi-omics protocol to study the spatial distribution and provide high resolution metabolic maps for each cell type, and which can be matched to both histopathology and MR Imaging. Multi-disciplinary platforms on large cohorts are needed to explore the clinical potential of the suggested molecular mechanisms. I expect that this ambitious proposal will address the diagnostic challenges of PCa and will further inspire the clinic and scientific community to follow the multi-omics approach within diagnosis and cancer research.
Summary
Overtreatment in prostate cancer (PCa) is a burden for health care economy and for quality of life. Correct diagnosis of early stage PCa is challenging given the limitations of the currently available clinical tools and the biological understanding of PCa. In this inter-disciplinary project, I propose an innovative approach enabling several cutting-edge ‘omics’ technologies (spatial metabolomics, genomics, transcriptomics) as well as histopathology to be performed on the same tissue sample. My goal is to reveal the molecular mechanisms of novel, but also promising metabolite biomarkers (citrate, polyamines, succinate and zinc) and their connection to recurrence, tissue heterogeneity and immune responses in complex human tissues. Such markers can personalize PCa diagnosis, open up new treatment strategies and fundamentally change the view of how to analyze tissue samples in the future. Furthermore, I want to demonstrate that citrate and polyamines are reliable prognostic markers that can be analyzed both in tissue and in patients in vivo by MR spectroscopic imaging. This work is made possible by the availability of high-quality fresh frozen tissue biobanks of prostatectomy biopsies with 5-10 years of follow-up data (N=1000)/slices (N=1000) and targeted in vivo snap-shot biopsies from clinical MR guided procedures (N=100). Among other techniques, I will implement high speed MALDI imaging (RapifleX MALDI TissueTyper) to the multi-omics protocol to study the spatial distribution and provide high resolution metabolic maps for each cell type, and which can be matched to both histopathology and MR Imaging. Multi-disciplinary platforms on large cohorts are needed to explore the clinical potential of the suggested molecular mechanisms. I expect that this ambitious proposal will address the diagnostic challenges of PCa and will further inspire the clinic and scientific community to follow the multi-omics approach within diagnosis and cancer research.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym SCARABEE
Project Scalable inference algorithms for Bayesian evolutionary epidemiology
Researcher (PI) Jukka CORANDER
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Advanced Grant (AdG), LS8, ERC-2016-ADG
Summary Advances in sequencing technologies are currently providing an unprecedented opportunity to a detailed discovery of the mechanisms involved in the evolution and spread of microbes causing human infectious disease. Simultaneously the developers of statistical methods face an enormous challenge to cope with the wealth of data brought by this opportunity. We have very recently demonstrated the ability of our advanced computational approaches to deliver breakthroughs in understanding pathogen evolution and transmission in numerous highlight results published in Science, PNAS and top-ranking Nature journals. The rise of microbial Big Data gives a promise of a giant leap in making causal discoveries, however, the existing statistical methods are neither able to cope with the size and complexity of the emerging data sets nor designed to answer the novel biological questions they enable. To fulfil the promise of giant leaps SCARABEE will leverage scalable inference methods by a unique combination of machine learning algorithms and Bayesian statistical models for evolutionary epidemiology. We focus on central biological questions about adaptation, epistasis, genome evolution and transmission of microbes causing infectious disease. The Big Data combined with the novel inference methods will make it possible to answer a multitude of important questions that remain currently intractable. Through our close collaboration with the leading research centres in infectious disease epidemiology and genomics we expect the SCARABEE project to considerably advance understanding of the evolution and transmission of numerous pathogens that pose a major threat to human health, which will be important for reducing their disease burden in the future. Large-scale biological data will be used to benchmark the developed methods, which will be made publicly available as free software packages to benefit the wide community of microbiologists and infectious disease epidemiologists.
Summary
Advances in sequencing technologies are currently providing an unprecedented opportunity to a detailed discovery of the mechanisms involved in the evolution and spread of microbes causing human infectious disease. Simultaneously the developers of statistical methods face an enormous challenge to cope with the wealth of data brought by this opportunity. We have very recently demonstrated the ability of our advanced computational approaches to deliver breakthroughs in understanding pathogen evolution and transmission in numerous highlight results published in Science, PNAS and top-ranking Nature journals. The rise of microbial Big Data gives a promise of a giant leap in making causal discoveries, however, the existing statistical methods are neither able to cope with the size and complexity of the emerging data sets nor designed to answer the novel biological questions they enable. To fulfil the promise of giant leaps SCARABEE will leverage scalable inference methods by a unique combination of machine learning algorithms and Bayesian statistical models for evolutionary epidemiology. We focus on central biological questions about adaptation, epistasis, genome evolution and transmission of microbes causing infectious disease. The Big Data combined with the novel inference methods will make it possible to answer a multitude of important questions that remain currently intractable. Through our close collaboration with the leading research centres in infectious disease epidemiology and genomics we expect the SCARABEE project to considerably advance understanding of the evolution and transmission of numerous pathogens that pose a major threat to human health, which will be important for reducing their disease burden in the future. Large-scale biological data will be used to benchmark the developed methods, which will be made publicly available as free software packages to benefit the wide community of microbiologists and infectious disease epidemiologists.
Max ERC Funding
2 499 961 €
Duration
Start date: 2017-08-01, End date: 2022-07-31
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
