Project acronym A-DIET
Project Metabolomics based biomarkers of dietary intake- new tools for nutrition research
Researcher (PI) Lorraine Brennan
Host Institution (HI) UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Call Details Consolidator Grant (CoG), LS7, ERC-2014-CoG
Summary In todays advanced technological world, we can track the exact movement of individuals, analyse their genetic makeup and predict predisposition to certain diseases. However, we are unable to accurately assess an individual’s dietary intake. This is without a doubt one of the main stumbling blocks in assessing the link between diet and disease/health. The present proposal (A-DIET) will address this issue with the overarching objective to develop novel strategies for assessment of dietary intake.
Using approaches to (1) identify biomarkers of specific foods (2) classify people into dietary patterns (nutritypes) and (3) develop a tool for integration of dietary and biomarker data, A-DIET has the potential to dramatically enhance our ability to accurately assess dietary intake. The ultimate output from A-DIET will be a dietary assessment tool which can be used to obtain an accurate assessment of dietary intake by combining dietary and biomarker data which in turn will allow investigations into relationships between diet, health and disease. New biomarkers of specific foods will be identified and validated using intervention studies and metabolomic analyses. Methods will be developed to classify individuals into dietary patterns based on biomarker/metabolomic profiles thus demonstrating the novel concept of nutritypes. Strategies for integration of dietary and biomarker data will be developed and translated into a tool that will be made available to the wider scientific community.
Advances made in A-DIET will enable nutrition epidemiologist’s to properly examine the relationship between diet and disease and develop clear public health messages with regard to diet and health. Additionally results from A-DIET will allow researchers to accurately assess people’s diet and implement health promotion strategies and enable dieticians in a clinical environment to assess compliance to therapeutic diets such as adherence to a high fibre diet or a gluten free diet.
Summary
In todays advanced technological world, we can track the exact movement of individuals, analyse their genetic makeup and predict predisposition to certain diseases. However, we are unable to accurately assess an individual’s dietary intake. This is without a doubt one of the main stumbling blocks in assessing the link between diet and disease/health. The present proposal (A-DIET) will address this issue with the overarching objective to develop novel strategies for assessment of dietary intake.
Using approaches to (1) identify biomarkers of specific foods (2) classify people into dietary patterns (nutritypes) and (3) develop a tool for integration of dietary and biomarker data, A-DIET has the potential to dramatically enhance our ability to accurately assess dietary intake. The ultimate output from A-DIET will be a dietary assessment tool which can be used to obtain an accurate assessment of dietary intake by combining dietary and biomarker data which in turn will allow investigations into relationships between diet, health and disease. New biomarkers of specific foods will be identified and validated using intervention studies and metabolomic analyses. Methods will be developed to classify individuals into dietary patterns based on biomarker/metabolomic profiles thus demonstrating the novel concept of nutritypes. Strategies for integration of dietary and biomarker data will be developed and translated into a tool that will be made available to the wider scientific community.
Advances made in A-DIET will enable nutrition epidemiologist’s to properly examine the relationship between diet and disease and develop clear public health messages with regard to diet and health. Additionally results from A-DIET will allow researchers to accurately assess people’s diet and implement health promotion strategies and enable dieticians in a clinical environment to assess compliance to therapeutic diets such as adherence to a high fibre diet or a gluten free diet.
Max ERC Funding
1 995 548 €
Duration
Start date: 2015-08-01, End date: 2020-07-31
Project acronym AdaptoSCOPE
Project Using cis-regulatory mutations to highlight polygenic adaptation in natural plant systems
Researcher (PI) Juliette de Meaux
Host Institution (HI) UNIVERSITAET ZU KOELN
Call Details Consolidator Grant (CoG), LS8, ERC-2014-CoG
Summary The goal of this project is to demonstrate that novel aspects of the molecular basis of Darwinian adaptation can be discovered if the polygenic basis of adaptation is taken into account. This project will use the genome-wide distribution of cis-regulatory variants to discover the molecular pathways that are optimized during adaptation via accumulation of small effect mutations. Current approaches include scans for outlier genes with strong population genetics signatures of selection, or large effect QTL associating with fitness. They can only reveal a small subset of the molecular changes recruited along adaptive paths. Here, instead, the distribution of small effect mutations will be used to make inferences on the targets of polygenic adaptation across divergent populations in each of the two closely related species, A. thaliana and A. lyrata. These species are both found at diverse latitudes and show sign of local adaptation to climatic differences. Mutations affecting cis-regulation will be identified in leaves of plants exposed to various temperature regimes triggering phenotypic responses of adaptive relevance. Their distribution in clusters of functionally connected genes will be quantified. The phylogeographic differences in the distribution of the mutations will be used to disentangle neutral from adaptive clusters of functionally connected genes in each of the two species. This project will identify the molecular pathways subjected collectively to natural selection and provide a completely novel view on adaptive landscapes. It will further examine whether local adaptation occurs by convergent evolution of molecular systems in plants. This approach has the potential to find broad applications in ecology and agriculture.
Summary
The goal of this project is to demonstrate that novel aspects of the molecular basis of Darwinian adaptation can be discovered if the polygenic basis of adaptation is taken into account. This project will use the genome-wide distribution of cis-regulatory variants to discover the molecular pathways that are optimized during adaptation via accumulation of small effect mutations. Current approaches include scans for outlier genes with strong population genetics signatures of selection, or large effect QTL associating with fitness. They can only reveal a small subset of the molecular changes recruited along adaptive paths. Here, instead, the distribution of small effect mutations will be used to make inferences on the targets of polygenic adaptation across divergent populations in each of the two closely related species, A. thaliana and A. lyrata. These species are both found at diverse latitudes and show sign of local adaptation to climatic differences. Mutations affecting cis-regulation will be identified in leaves of plants exposed to various temperature regimes triggering phenotypic responses of adaptive relevance. Their distribution in clusters of functionally connected genes will be quantified. The phylogeographic differences in the distribution of the mutations will be used to disentangle neutral from adaptive clusters of functionally connected genes in each of the two species. This project will identify the molecular pathways subjected collectively to natural selection and provide a completely novel view on adaptive landscapes. It will further examine whether local adaptation occurs by convergent evolution of molecular systems in plants. This approach has the potential to find broad applications in ecology and agriculture.
Max ERC Funding
1 683 120 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym ALH
Project Alternative life histories: linking genes to phenotypes to demography
Researcher (PI) Thomas Eric Reed
Host Institution (HI) UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK
Call Details Starting Grant (StG), LS8, ERC-2014-STG
Summary Understanding how and why individuals develop strikingly different life histories is a major goal in evolutionary biology. It is also a prerequisite for conserving important biodiversity within species and predicting the impacts of environmental change on populations. The aim of my study is to examine a key threshold phenotypic trait (alternative migratory tactics) in a series of large scale laboratory and field experiments, integrating several previously independent perspectives from evolutionary ecology, ecophysiology and genomics, to produce a downstream predictive model. My chosen study species, the brown trout Salmo trutta, has an extensive history of genetic and experimental work and exhibits ‘partial migration’: individuals either migrate to sea (‘sea trout’) or remain in freshwater their whole lives. Recent advances in molecular parentage assignment, quantitative genetics and genomics (next generation sequencing and bioinformatics) will allow unprecedented insight into how alternative life history phenotypes are moulded by the interaction between genes and environment. To provide additional mechanistic understanding of these processes, the balance between metabolic requirements during growth and available extrinsic resources will be investigated as the major physiological driver of migratory behaviour. Together these results will be used to develop a predictive model to explore the consequences of rapid environmental change, accounting for the effects of genetics and environment on phenotype and on population demographics. In addition to their value for conservation and management of an iconic and key species in European freshwaters and coastal seas, these results will generate novel insight into the evolution of migratory behaviour generally, providing a text book example of how alternative life histories are shaped and maintained in wild populations.
Summary
Understanding how and why individuals develop strikingly different life histories is a major goal in evolutionary biology. It is also a prerequisite for conserving important biodiversity within species and predicting the impacts of environmental change on populations. The aim of my study is to examine a key threshold phenotypic trait (alternative migratory tactics) in a series of large scale laboratory and field experiments, integrating several previously independent perspectives from evolutionary ecology, ecophysiology and genomics, to produce a downstream predictive model. My chosen study species, the brown trout Salmo trutta, has an extensive history of genetic and experimental work and exhibits ‘partial migration’: individuals either migrate to sea (‘sea trout’) or remain in freshwater their whole lives. Recent advances in molecular parentage assignment, quantitative genetics and genomics (next generation sequencing and bioinformatics) will allow unprecedented insight into how alternative life history phenotypes are moulded by the interaction between genes and environment. To provide additional mechanistic understanding of these processes, the balance between metabolic requirements during growth and available extrinsic resources will be investigated as the major physiological driver of migratory behaviour. Together these results will be used to develop a predictive model to explore the consequences of rapid environmental change, accounting for the effects of genetics and environment on phenotype and on population demographics. In addition to their value for conservation and management of an iconic and key species in European freshwaters and coastal seas, these results will generate novel insight into the evolution of migratory behaviour generally, providing a text book example of how alternative life histories are shaped and maintained in wild populations.
Max ERC Funding
1 499 202 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym ANICOLEVO
Project Animal coloration through deep time: evolutionary novelty, homology and taphonomy
Researcher (PI) Maria McNamara
Host Institution (HI) UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK
Call Details Starting Grant (StG), LS8, ERC-2014-STG
Summary What does the fossil record tell us about the evolution of colour in animals through deep time? Evidence of colour in fossils can inform on the visual signalling strategies used by ancient animals. Research to date often has a narrow focus, lacks a broad phylogenetic and temporal context, and rarely incorporates information on taphonomy. This proposal represents a bold new holistic approach to the study of fossil colour: it will couple powerful imaging- and chemical analytical techniques with a rigorous programme of fossilisation experiments simulating decay, burial, and transport, and analysis of fossils and their sedimentary context, to construct the first robust models for the evolution of colour in animals through deep time. The research will resolve the original integumentary colours of fossil higher vertebrates, and the original colours of fossil hair; the fossil record of non-melanin pigments in feathers and insects; the biological significance of monotonal patterning in fossil insects; and the evolutionary history of scales and 3D photonic crystals in insects. Critically, the research will test, for the first time, whether evidence of fossil colour can solve broader evolutionary questions, e.g. the true affinities of enigmatic Cambrian chordate-like metazoans, and feather-like integumentary filaments in dinosaurs. The proposal entails construction of a dedicated experimental maturation laboratory for simulating the impact of burial on tissues. This laboratory will form the core of the world’s first integrated ‘experimental fossilisation facility’, consolidating the PI’s team as the global hub for fossil colour research. The research team comprises the PI, three postdoctoral researchers, and three PhD students, and will form an extensive research network via collaborations with 13 researchers from Europe and beyond. The project will reach out to diverse scientists and will inspire a positive attitude to science among the general public and policymakers alike.
Summary
What does the fossil record tell us about the evolution of colour in animals through deep time? Evidence of colour in fossils can inform on the visual signalling strategies used by ancient animals. Research to date often has a narrow focus, lacks a broad phylogenetic and temporal context, and rarely incorporates information on taphonomy. This proposal represents a bold new holistic approach to the study of fossil colour: it will couple powerful imaging- and chemical analytical techniques with a rigorous programme of fossilisation experiments simulating decay, burial, and transport, and analysis of fossils and their sedimentary context, to construct the first robust models for the evolution of colour in animals through deep time. The research will resolve the original integumentary colours of fossil higher vertebrates, and the original colours of fossil hair; the fossil record of non-melanin pigments in feathers and insects; the biological significance of monotonal patterning in fossil insects; and the evolutionary history of scales and 3D photonic crystals in insects. Critically, the research will test, for the first time, whether evidence of fossil colour can solve broader evolutionary questions, e.g. the true affinities of enigmatic Cambrian chordate-like metazoans, and feather-like integumentary filaments in dinosaurs. The proposal entails construction of a dedicated experimental maturation laboratory for simulating the impact of burial on tissues. This laboratory will form the core of the world’s first integrated ‘experimental fossilisation facility’, consolidating the PI’s team as the global hub for fossil colour research. The research team comprises the PI, three postdoctoral researchers, and three PhD students, and will form an extensive research network via collaborations with 13 researchers from Europe and beyond. The project will reach out to diverse scientists and will inspire a positive attitude to science among the general public and policymakers alike.
Max ERC Funding
1 562 000 €
Duration
Start date: 2016-01-01, End date: 2020-12-31
Project acronym BIOELECPRO
Project Frontier Research on the Dielectric Properties of Biological Tissue
Researcher (PI) Martin James O'Halloran
Host Institution (HI) NATIONAL UNIVERSITY OF IRELAND GALWAY
Call Details Starting Grant (StG), LS7, ERC-2014-STG
Summary The dielectric properties of biological tissues are of fundamental importance to the understanding of the interaction of electromagnetic fields with the human body. These properties are used to determine the safety of electronic devices, and in the design, development and refinement of electromagnetic medical imaging and therapeutic devices. Many historical studies have aimed to establish the dielectric properties of a broad range of tissues. A growing number of recent studies have sought to more accurately estimate these dielectric properties by standardising measurement procedures, and in some cases, measuring the dielectric properties in-vivo. However, these studies have often produced results in direct conflict with historical studies, casting doubt on the accuracy of the currently utilised dielectric properties. At best, this uncertainty could significantly delay the development of electromagnetic imaging or therapeutic medical devices. At worst, the health dangers of electromagnetic radiation could be under-estimated. The applicant will embark upon frontier research to develop improved methods and standards for the measurement of the dielectric properties of biological tissue. The research programme will accelerate the design and development of electromagnetic imaging and therapeutic devices, at a time when the technology is gaining significant momentum. The primary objective of the research is to develop a deep understanding of the fundamental factors which contribute to errors in dielectric property measurement. These factors will include in-vivo/ex-vivo measurements and dielectric measurement method used, amongst many others. Secondly, a new open-access repository of dielectric measurements will be created based on a greatly enhanced understanding of the mechanisms underlying dielectric property measurement. Finally, new electromagnetic-based imaging and therapeutic medical devices will be investigated, based on the solid foundation of dielectric data.
Summary
The dielectric properties of biological tissues are of fundamental importance to the understanding of the interaction of electromagnetic fields with the human body. These properties are used to determine the safety of electronic devices, and in the design, development and refinement of electromagnetic medical imaging and therapeutic devices. Many historical studies have aimed to establish the dielectric properties of a broad range of tissues. A growing number of recent studies have sought to more accurately estimate these dielectric properties by standardising measurement procedures, and in some cases, measuring the dielectric properties in-vivo. However, these studies have often produced results in direct conflict with historical studies, casting doubt on the accuracy of the currently utilised dielectric properties. At best, this uncertainty could significantly delay the development of electromagnetic imaging or therapeutic medical devices. At worst, the health dangers of electromagnetic radiation could be under-estimated. The applicant will embark upon frontier research to develop improved methods and standards for the measurement of the dielectric properties of biological tissue. The research programme will accelerate the design and development of electromagnetic imaging and therapeutic devices, at a time when the technology is gaining significant momentum. The primary objective of the research is to develop a deep understanding of the fundamental factors which contribute to errors in dielectric property measurement. These factors will include in-vivo/ex-vivo measurements and dielectric measurement method used, amongst many others. Secondly, a new open-access repository of dielectric measurements will be created based on a greatly enhanced understanding of the mechanisms underlying dielectric property measurement. Finally, new electromagnetic-based imaging and therapeutic medical devices will be investigated, based on the solid foundation of dielectric data.
Max ERC Funding
1 499 329 €
Duration
Start date: 2015-10-01, End date: 2020-09-30
Project acronym BREATHE
Project Biochemically modified messenger RNA encoding nucleases for in vivo gene correction of severe inherited lung diseases
Researcher (PI) Michael Kormann
Host Institution (HI) EBERHARD KARLS UNIVERSITAET TUEBINGEN
Call Details Starting Grant (StG), LS7, ERC-2014-STG
Summary Surfactant Protein B (SP-B) deficiency and Cystic Fibrosis (CF) are severe, fatal inherited diseases affecting the lungs of ten thousands of people, for which there is currently no available cure. Although gene therapy is a promising therapeutic approach, various technical problems, including numerous physical and immune-mediated barriers, have prevented successful application to date. My recent studies were the first to demonstrate the life-saving efficacy of repeated pulmonary delivery of chemically modified messenger RNA (mRNA) in a mouse model of congenital SP-B deficiency. By incorporating balanced amounts of modified nucleotides to mimic endogenous transcripts, I developed a safe and therapeutically efficient vehicle for lung transfection that eliminates the risk of genomic integration commonly associated with DNA-based vectors. I also assessed the delivery of mRNA-encoded site-specific nucleases to the lung to facilitate targeted gene correction of the underlying disease-causing mutations. In comprehensive studies, we show that a single application of nucleases encoded by nucleotide-modified RNA (nec-mRNA) can generate in vivo correction of terminally differentiated alveolar type II cells, which more than quadrupled the life span of SP-B deficient mice. Together with my working group, I aim to further develop this technology to enhance the efficiency and safety of nec-mRNA-mediated in vivo lung stem cell targeting, providing an ultimate cure by permanent correction. Specifically, we will test this approach in humanized mouse models of SP-B deficiency and CF. Developing and genetically engineering humanized models in vivo will be a critical step towards the safe translation of mRNA based nuclease technology to the clinic. With my competitive edge in lung-transfection technology and strong data, I feel that my group is uniquely suited to achieve these goals and to make a highly valuable contribution to the development of an efficient treatment.
Summary
Surfactant Protein B (SP-B) deficiency and Cystic Fibrosis (CF) are severe, fatal inherited diseases affecting the lungs of ten thousands of people, for which there is currently no available cure. Although gene therapy is a promising therapeutic approach, various technical problems, including numerous physical and immune-mediated barriers, have prevented successful application to date. My recent studies were the first to demonstrate the life-saving efficacy of repeated pulmonary delivery of chemically modified messenger RNA (mRNA) in a mouse model of congenital SP-B deficiency. By incorporating balanced amounts of modified nucleotides to mimic endogenous transcripts, I developed a safe and therapeutically efficient vehicle for lung transfection that eliminates the risk of genomic integration commonly associated with DNA-based vectors. I also assessed the delivery of mRNA-encoded site-specific nucleases to the lung to facilitate targeted gene correction of the underlying disease-causing mutations. In comprehensive studies, we show that a single application of nucleases encoded by nucleotide-modified RNA (nec-mRNA) can generate in vivo correction of terminally differentiated alveolar type II cells, which more than quadrupled the life span of SP-B deficient mice. Together with my working group, I aim to further develop this technology to enhance the efficiency and safety of nec-mRNA-mediated in vivo lung stem cell targeting, providing an ultimate cure by permanent correction. Specifically, we will test this approach in humanized mouse models of SP-B deficiency and CF. Developing and genetically engineering humanized models in vivo will be a critical step towards the safe translation of mRNA based nuclease technology to the clinic. With my competitive edge in lung-transfection technology and strong data, I feel that my group is uniquely suited to achieve these goals and to make a highly valuable contribution to the development of an efficient treatment.
Max ERC Funding
1 497 125 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym CleverGenes
Project Novel Gene Therapy Based on the Activation of Endogenous Genes for the Treatment of Ischemia - Concepts of endogenetherapy, release of promoter pausing, promoter-targeted ncRNAs and nuclear RNAi
Researcher (PI) Seppo Ylä-Herttuala
Host Institution (HI) ITA-SUOMEN YLIOPISTO
Call Details Advanced Grant (AdG), LS7, ERC-2014-ADG
Summary Background: Therapeutic angiogenesis with vascular endothelial growth factors (VEGFs) has great potential to become a novel, minimally invasive new treatment for a large number of patients with severe myocardial ischemia. However, this requires development of new technology. Advancing state-of-the-art: We propose a paradigm shift in gene therapy for chronic ischemia by activating endogenous VEGF-A,-B and -C genes and angiogenic transcription programs from the native promoters instead of gene transfer of exogenous cDNA to target tissues. We will develop a new platform technology (endogenetherapy) based on our novel concept of the release of promoter pausing and new promoter-targeted upregulating short hairpinRNAs, tissue-specific superenhancerRNAs activating specific transcription centers involving gene clusters in different chromosomal regions, small circularRNAs formed from self-splicing exons-introns that can be regulated with oligonucleotides and small molecules such as metabolites, nuclear RNAi vectors and specific CRISPR/gRNAmutatedCas9-VP16 technology with an ability to target integration into genomic safe harbor sites. After preclinical studies in mice and in a newly developed chronic cardiac ischemia model in pigs with special emphasis on the analysis of clinically relevant blood flow, metabolic and functional outcomes based on MRI, ultrasound, photoacoustic and PET imaging, the best construct will be taken to a phase I clinical study in patients with severe myocardial ischemia. Since endogenetherapy also involves epigenetic changes, which are reversible and long-lasting, we expect to efficiently activate natural angiogenic programs. Significance: If successful, this approach will begin a new era in gene therapy. Since there is a clear lack of technology capable of targeted upregulation of endogenous genes, the novel endogenetherapy approach may become widely applicable beyond cardiovascular diseases also in other areas of medicine and biomedical research.
Summary
Background: Therapeutic angiogenesis with vascular endothelial growth factors (VEGFs) has great potential to become a novel, minimally invasive new treatment for a large number of patients with severe myocardial ischemia. However, this requires development of new technology. Advancing state-of-the-art: We propose a paradigm shift in gene therapy for chronic ischemia by activating endogenous VEGF-A,-B and -C genes and angiogenic transcription programs from the native promoters instead of gene transfer of exogenous cDNA to target tissues. We will develop a new platform technology (endogenetherapy) based on our novel concept of the release of promoter pausing and new promoter-targeted upregulating short hairpinRNAs, tissue-specific superenhancerRNAs activating specific transcription centers involving gene clusters in different chromosomal regions, small circularRNAs formed from self-splicing exons-introns that can be regulated with oligonucleotides and small molecules such as metabolites, nuclear RNAi vectors and specific CRISPR/gRNAmutatedCas9-VP16 technology with an ability to target integration into genomic safe harbor sites. After preclinical studies in mice and in a newly developed chronic cardiac ischemia model in pigs with special emphasis on the analysis of clinically relevant blood flow, metabolic and functional outcomes based on MRI, ultrasound, photoacoustic and PET imaging, the best construct will be taken to a phase I clinical study in patients with severe myocardial ischemia. Since endogenetherapy also involves epigenetic changes, which are reversible and long-lasting, we expect to efficiently activate natural angiogenic programs. Significance: If successful, this approach will begin a new era in gene therapy. Since there is a clear lack of technology capable of targeted upregulation of endogenous genes, the novel endogenetherapy approach may become widely applicable beyond cardiovascular diseases also in other areas of medicine and biomedical research.
Max ERC Funding
2 437 500 €
Duration
Start date: 2015-11-01, End date: 2020-10-31
Project acronym COMBIOSCOPY
Project Computational Biophotonics for Endoscopic Cancer Diagnosis and Therapy
Researcher (PI) Lena Maier-Hein
Host Institution (HI) DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Call Details Starting Grant (StG), LS7, ERC-2014-STG
Summary Key challenges in endoscopic tumor diagnosis and therapy consist of the detection and discrimination of malignant tissue as well as the precise navigation of medical instruments. Currently, a low level of sensitivity and specificity in tumor detection and lack of global orientation lead to both over- and undertreatment, tumor recurrence, intra-operative complications, and high costs. The goal of this multidisciplinary project is to revolutionize clinical endoscopic imaging based on the systematic integration of two new but independant fields of research up until this point: Biophotonics and computer-assisted interventions (COMputational BIOphotonics in endoSCOPY).
For the first time, quantitative multi-modal imaging biomarkers based on structural and functional data are being developed to enhance the physician’s view by providing information that cannot be seen with the naked eye. To this extent, white light images co-registered with multispectral optical and photoacoustic images will be processed in a combined manner to dynamically reconstruct not only the visible surface in 3D but also subsurface anatomical and functional detail such as 3D vessel topology, blood volume and oxygenation. Spatio-temporal registration of multi-modal data acquired before and during the procedure will enable (1) the highly specific local tissue classification and discrimination based on tissue shape, texture, function and radiological contrast imagery as well as (2) global context-aware instrument guidance.
This innovative approach to radiation-free real-time imaging will be implemented and evaluated by means of computer-assisted colonoscopy and laparoscopy. The potential socioeconomic impact of providing high precision minimally-invasive tumor diagnosis and therapy at low cost is extremely high.
Summary
Key challenges in endoscopic tumor diagnosis and therapy consist of the detection and discrimination of malignant tissue as well as the precise navigation of medical instruments. Currently, a low level of sensitivity and specificity in tumor detection and lack of global orientation lead to both over- and undertreatment, tumor recurrence, intra-operative complications, and high costs. The goal of this multidisciplinary project is to revolutionize clinical endoscopic imaging based on the systematic integration of two new but independant fields of research up until this point: Biophotonics and computer-assisted interventions (COMputational BIOphotonics in endoSCOPY).
For the first time, quantitative multi-modal imaging biomarkers based on structural and functional data are being developed to enhance the physician’s view by providing information that cannot be seen with the naked eye. To this extent, white light images co-registered with multispectral optical and photoacoustic images will be processed in a combined manner to dynamically reconstruct not only the visible surface in 3D but also subsurface anatomical and functional detail such as 3D vessel topology, blood volume and oxygenation. Spatio-temporal registration of multi-modal data acquired before and during the procedure will enable (1) the highly specific local tissue classification and discrimination based on tissue shape, texture, function and radiological contrast imagery as well as (2) global context-aware instrument guidance.
This innovative approach to radiation-free real-time imaging will be implemented and evaluated by means of computer-assisted colonoscopy and laparoscopy. The potential socioeconomic impact of providing high precision minimally-invasive tumor diagnosis and therapy at low cost is extremely high.
Max ERC Funding
1 499 699 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
Project acronym COSIP
Project Clarifying Optimal Sodium Intake Project
Researcher (PI) Martin James O'Donnell
Host Institution (HI) NATIONAL UNIVERSITY OF IRELAND GALWAY
Call Details Starting Grant (StG), LS7, ERC-2014-STG
Summary Hypertension is a leading risk factor for cardiovascular disease (CVD) globally, accounting for 25-35% of the population-attributable fraction. Sodium (salt) intake is a key determinant of blood pressure, and reducing sodium intake has emerged as an important target for population-based interventions to prevent CVD. However, there is considerable uncertainty about the optimal level of sodium (salt) intake that is associated with lowest CVD risk, and whether optimal levels differ for different populations and individuals. In this proposal, we will answer key fundamental research questions about the association of sodium intake with blood pressure and CVD risk. Our research challenges current guideline recommendations of low-sodium intake for all populations. Specifically, we will: a) determine whether sustained (long-term) low sodium intake is associated with beneficial (or adverse) effects on established and novel CV biomarkers. b) explore whether inter-daily ‘pattern’ of sodium intake is an important determinant of 24-hour blood pressure pattern; c) determine whether the association between sodium intake and CVD varies by ethnicity, sex, age, other dietary factors (e.g. potassium intake), or other factors in 2 large international epidemiologic studies (PURE and INTERSTROKE; n>125,000 individuals). d) quantify the population-attributable fraction of excess sodium intake on global burden of CVD (stroke, myocardial infarction, heart failure and CV death), and model the potential impact of various population-based approaches to reducing sodium intake; e) determine whether sodium intake is associated with other vascular-related clinical conditions, namely including atrial fibrillation, cognitive impairment and falls (providing novel information); f) determine whether genetic variants associated with ‘salt sensitivity’ and hypertension are association with blood pressure and stroke, and whether these associations are modified by sodium intake.
Summary
Hypertension is a leading risk factor for cardiovascular disease (CVD) globally, accounting for 25-35% of the population-attributable fraction. Sodium (salt) intake is a key determinant of blood pressure, and reducing sodium intake has emerged as an important target for population-based interventions to prevent CVD. However, there is considerable uncertainty about the optimal level of sodium (salt) intake that is associated with lowest CVD risk, and whether optimal levels differ for different populations and individuals. In this proposal, we will answer key fundamental research questions about the association of sodium intake with blood pressure and CVD risk. Our research challenges current guideline recommendations of low-sodium intake for all populations. Specifically, we will: a) determine whether sustained (long-term) low sodium intake is associated with beneficial (or adverse) effects on established and novel CV biomarkers. b) explore whether inter-daily ‘pattern’ of sodium intake is an important determinant of 24-hour blood pressure pattern; c) determine whether the association between sodium intake and CVD varies by ethnicity, sex, age, other dietary factors (e.g. potassium intake), or other factors in 2 large international epidemiologic studies (PURE and INTERSTROKE; n>125,000 individuals). d) quantify the population-attributable fraction of excess sodium intake on global burden of CVD (stroke, myocardial infarction, heart failure and CV death), and model the potential impact of various population-based approaches to reducing sodium intake; e) determine whether sodium intake is associated with other vascular-related clinical conditions, namely including atrial fibrillation, cognitive impairment and falls (providing novel information); f) determine whether genetic variants associated with ‘salt sensitivity’ and hypertension are association with blood pressure and stroke, and whether these associations are modified by sodium intake.
Max ERC Funding
1 499 431 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym CVI_ADAPT
Project Unraveling the history of adaptation in an island model: Cape Verde Arabidopsis
Researcher (PI) Angela Hancock
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Starting Grant (StG), LS8, ERC-2014-STG
Summary Islands have played a pivotal role in evolutionary theory since Darwin and Wallace. Due to their isolation, they represent natural laboratories, providing uncomplicated microcosms where fundamental principles of the evolutionary process can be revealed. One area where island systems can provide a crucial advance is in evolutionary genetics. Here, a primary goal is to reconstruct the mechanisms, mode and tempo of the evolutionary process by identifying specific adaptive functional variants and studying the historical dynamics of these in nature. However, even with recent advances in tools and technologies (e.g., affordable genome-wide sequencing, developments in genome manipulation), the complexity of most natural systems makes this a challenging task.
The proposed research launches a program that employs a unique set of thale cress (Arabidopsis) samples from intriguing populations at the edge of the species range (Cape Verde Islands) to comprehensively characterize the adaptive process in a tractable and ecologically relevant island system. This collection represents the first population sample from this region, where a single individual was collected 30 years ago and has long been an enigma due to its remarkable phenotypic and genetic divergence. We will combine field monitoring, population genetic analyses, trait mapping, powerful new genome editing technology (CRISPR), and spatially explicit modeling to reconstruct the history of the adaptive process in exceptional detail. Moreover, synthesizing our results in the context of biological networks will provide the opportunity to decipher how epistasis and pleiotropy impacted adaptive trajectories. By applying the wealth of tools available in Arabidopsis thaliana to this intriguing natural population, we will uncover general principles of adaptation and produce a roadmap and toolkit for future research in diverse systems to predict outcomes of environmental fluctuations and longer-term changes.
Summary
Islands have played a pivotal role in evolutionary theory since Darwin and Wallace. Due to their isolation, they represent natural laboratories, providing uncomplicated microcosms where fundamental principles of the evolutionary process can be revealed. One area where island systems can provide a crucial advance is in evolutionary genetics. Here, a primary goal is to reconstruct the mechanisms, mode and tempo of the evolutionary process by identifying specific adaptive functional variants and studying the historical dynamics of these in nature. However, even with recent advances in tools and technologies (e.g., affordable genome-wide sequencing, developments in genome manipulation), the complexity of most natural systems makes this a challenging task.
The proposed research launches a program that employs a unique set of thale cress (Arabidopsis) samples from intriguing populations at the edge of the species range (Cape Verde Islands) to comprehensively characterize the adaptive process in a tractable and ecologically relevant island system. This collection represents the first population sample from this region, where a single individual was collected 30 years ago and has long been an enigma due to its remarkable phenotypic and genetic divergence. We will combine field monitoring, population genetic analyses, trait mapping, powerful new genome editing technology (CRISPR), and spatially explicit modeling to reconstruct the history of the adaptive process in exceptional detail. Moreover, synthesizing our results in the context of biological networks will provide the opportunity to decipher how epistasis and pleiotropy impacted adaptive trajectories. By applying the wealth of tools available in Arabidopsis thaliana to this intriguing natural population, we will uncover general principles of adaptation and produce a roadmap and toolkit for future research in diverse systems to predict outcomes of environmental fluctuations and longer-term changes.
Max ERC Funding
1 609 375 €
Duration
Start date: 2015-11-01, End date: 2020-10-31
