Project acronym ZMOD
Project Blood Vessel Development and Homeostasis: Identification and Functional Analysis of Genetic Modifiers
Researcher (PI) Didier STAINIER
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Country Germany
Call Details Advanced Grant (AdG), LS3, ERC-2015-AdG
Summary The vascular system is a complex network of blood vessels that transports gases, nutrients and hormones throughout the organism. Most blood vessels that form during development and growth arise by the sprouting of new capillaries from pre-existing vessels, a process termed angiogenesis. An imbalance in angiogenesis contributes to the pathogenesis of numerous disease states: insufficient angiogenesis limits tissue recovery in ischemic disease, whereas stimulation of angiogenesis by cancer cells promotes tumor vascularization and growth. Angiogenesis inhibitors are already in clinical use for anti-tumor therapy; however, multiple reports of resistance are calling for the identification of additional targets. Furthermore, vascular malformations are a significant cause of morbidity and mortality. While the genetic basis for some vascular malformations is known, many genetic factors, including modifiers that affect the age-of-onset and severity of phenotypes, remain to be identified. Identifying modifier genes is important not only to fully assess genetic risk, but also to provide novel targets for therapy; however, identifying modifier genes has proven challenging. We recently uncovered a novel and simple way to identify modifier genes. By investigating gene and protein expression differences between knockout (mutant) and knockdown (antisense treated) zebrafish embryos, we found that mutations in specific genes, including some encoding angiogenic factors, lead to the upregulation of compensating (i.e., modifier) genes while knocking down these same genes does not. We hypothesize that the modifier genes identified through this approach in zebrafish also play important roles in humans. Thus, we will use this simple strategy to identify new genes that regulate vascular formation and homeostasis, and subsequently analyze their function in zebrafish as well as in mammalian models, as they are likely to play key roles in vascular development and disease.
Summary
The vascular system is a complex network of blood vessels that transports gases, nutrients and hormones throughout the organism. Most blood vessels that form during development and growth arise by the sprouting of new capillaries from pre-existing vessels, a process termed angiogenesis. An imbalance in angiogenesis contributes to the pathogenesis of numerous disease states: insufficient angiogenesis limits tissue recovery in ischemic disease, whereas stimulation of angiogenesis by cancer cells promotes tumor vascularization and growth. Angiogenesis inhibitors are already in clinical use for anti-tumor therapy; however, multiple reports of resistance are calling for the identification of additional targets. Furthermore, vascular malformations are a significant cause of morbidity and mortality. While the genetic basis for some vascular malformations is known, many genetic factors, including modifiers that affect the age-of-onset and severity of phenotypes, remain to be identified. Identifying modifier genes is important not only to fully assess genetic risk, but also to provide novel targets for therapy; however, identifying modifier genes has proven challenging. We recently uncovered a novel and simple way to identify modifier genes. By investigating gene and protein expression differences between knockout (mutant) and knockdown (antisense treated) zebrafish embryos, we found that mutations in specific genes, including some encoding angiogenic factors, lead to the upregulation of compensating (i.e., modifier) genes while knocking down these same genes does not. We hypothesize that the modifier genes identified through this approach in zebrafish also play important roles in humans. Thus, we will use this simple strategy to identify new genes that regulate vascular formation and homeostasis, and subsequently analyze their function in zebrafish as well as in mammalian models, as they are likely to play key roles in vascular development and disease.
Max ERC Funding
2 500 000 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym ZODIAC
Project Ancient Astral Science in Transformation
Researcher (PI) Antonius Joannes Hendrikus Ossendrijver
Host Institution (HI) FREIE UNIVERSITAET BERLIN
Country Germany
Call Details Advanced Grant (AdG), SH6, ERC-2019-ADG
Summary The introduction of the zodiac in Babylonia in the 5th century BCE was a turning point in the history of astral science - astronomy and astrology, scholarship and culture at large. The “zodiacal turn” was accompanied by a “mathematical turn” in astronomy and a “personal turn” in astrology. From Babylonia, zodiacal astral science spread to Egypt, the Greco-Roman world and beyond. In view of its entanglement with social practices, religious doctrines, philosophical theories and iconographic expressions, its global spread can be compared with that of Christianity, Islam, or Copernican astronomy. How did zodiacal astral science emerge, develop and spread to different ancient cultures and take root there? What explains the enormous success of this cross-cultural phenomenon? Until now, scholarship has failed to answer these questions, because crucial evidence has been ignored.
ZODIAC will develop an account based on the hypothesis that zodiacal astral science offered universally appealing, adaptable solutions to social, religious and political needs that emerged in multi-cultural empires. It achieve this with an interdisciplinary approach that pays full attention to all aspects that shape transmission by conceiving astral science as a package of entangled astronomical, astrological, mathematical and other practices. It wil carry out the first in-depth, comprehensive study of cross-cultural transformations in textual and iconographic sources, including pivotal groups of overlooked ones, to reveal strategies that foster acceptance in new contexts. The accuracy of ancient predictions will be cross-culturally analysed using modern astrophysics. Recent scholarship on ancient empires will contextualise astral science in a new framework that transcends microhistorical approaches. The new account will be developed in dialogue with existing models of innovation, transmission and theory change, thus connecting ancient astral science to contemporary narratives of globalisation.
Summary
The introduction of the zodiac in Babylonia in the 5th century BCE was a turning point in the history of astral science - astronomy and astrology, scholarship and culture at large. The “zodiacal turn” was accompanied by a “mathematical turn” in astronomy and a “personal turn” in astrology. From Babylonia, zodiacal astral science spread to Egypt, the Greco-Roman world and beyond. In view of its entanglement with social practices, religious doctrines, philosophical theories and iconographic expressions, its global spread can be compared with that of Christianity, Islam, or Copernican astronomy. How did zodiacal astral science emerge, develop and spread to different ancient cultures and take root there? What explains the enormous success of this cross-cultural phenomenon? Until now, scholarship has failed to answer these questions, because crucial evidence has been ignored.
ZODIAC will develop an account based on the hypothesis that zodiacal astral science offered universally appealing, adaptable solutions to social, religious and political needs that emerged in multi-cultural empires. It achieve this with an interdisciplinary approach that pays full attention to all aspects that shape transmission by conceiving astral science as a package of entangled astronomical, astrological, mathematical and other practices. It wil carry out the first in-depth, comprehensive study of cross-cultural transformations in textual and iconographic sources, including pivotal groups of overlooked ones, to reveal strategies that foster acceptance in new contexts. The accuracy of ancient predictions will be cross-culturally analysed using modern astrophysics. Recent scholarship on ancient empires will contextualise astral science in a new framework that transcends microhistorical approaches. The new account will be developed in dialogue with existing models of innovation, transmission and theory change, thus connecting ancient astral science to contemporary narratives of globalisation.
Max ERC Funding
2 499 779 €
Duration
Start date: 2021-04-01, End date: 2026-03-31
Project acronym ZoomDeep
Project Zooming in on the core-mantle boundary
Researcher (PI) Sanne COTTAAR
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Starting Grant (StG), PE10, ERC-2018-STG
Summary The core-mantle boundary (CMB) is the interface between the liquid iron core and the silicate solid mantle, and is the most significant internal boundary of the Earth. The core and the mantle interact across the boundary through transfer of heat and material, and various coupling mechanisms. While the nature and variability of these interactions remains uncertain, they strongly affect the convection in the mantle, responsible for plate tectonics and intra-plate volcanism, as well as the much more vigorous convection in the core, responsible for the geodynamo. Constraining the interactions at the CMB is crucial to understanding physical processes in the deep Earth and the thermal, compositional, and dynamical evolution of the Earth.
The CMB interactions are strongly controlled by heterogeneous structures on or near the boundary. On the mantle side, seismological imaging has observed slow velocity layering and patches, but their physical significance remains uncertain, and it is unclear whether they represent global or local features. Turning to the core, suggestions of a stable light-element-enriched layer have been made. The estimated thickness of such a layer varies from 40 to 450 km, and the origin of the inferred light elements is heavily debated.
In ZoomDeep, I propose innovative seismic techniques to image the structure near the CMB with unprecedented resolution. One technique, dubbed 'the Frequency Fan', will be newly developed, while another technique has recently been successfully applied at the Earth's surface and will be adapted to the CMB. ZoomDeep will lead to the first high-resolution maps of the structures near the CMB and will specifically focus on the roots of mantle upwellings beneath volcanic hotspots. The implications of these maps on fundamental questions impacting core and mantle dynamics will be assessed in multi-disciplinary approaches. The results of this work will transform our understanding of the dynamics and evolution of the Earth.
Summary
The core-mantle boundary (CMB) is the interface between the liquid iron core and the silicate solid mantle, and is the most significant internal boundary of the Earth. The core and the mantle interact across the boundary through transfer of heat and material, and various coupling mechanisms. While the nature and variability of these interactions remains uncertain, they strongly affect the convection in the mantle, responsible for plate tectonics and intra-plate volcanism, as well as the much more vigorous convection in the core, responsible for the geodynamo. Constraining the interactions at the CMB is crucial to understanding physical processes in the deep Earth and the thermal, compositional, and dynamical evolution of the Earth.
The CMB interactions are strongly controlled by heterogeneous structures on or near the boundary. On the mantle side, seismological imaging has observed slow velocity layering and patches, but their physical significance remains uncertain, and it is unclear whether they represent global or local features. Turning to the core, suggestions of a stable light-element-enriched layer have been made. The estimated thickness of such a layer varies from 40 to 450 km, and the origin of the inferred light elements is heavily debated.
In ZoomDeep, I propose innovative seismic techniques to image the structure near the CMB with unprecedented resolution. One technique, dubbed 'the Frequency Fan', will be newly developed, while another technique has recently been successfully applied at the Earth's surface and will be adapted to the CMB. ZoomDeep will lead to the first high-resolution maps of the structures near the CMB and will specifically focus on the roots of mantle upwellings beneath volcanic hotspots. The implications of these maps on fundamental questions impacting core and mantle dynamics will be assessed in multi-disciplinary approaches. The results of this work will transform our understanding of the dynamics and evolution of the Earth.
Max ERC Funding
1 407 784 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym ZOOMecular
Project Read the fine print: Zooming into paleoenvironmental and biogeochemical processes through molecular imaging of biomarker distributions in sediments
Researcher (PI) Kai-Uwe Hinrichs
Host Institution (HI) UNIVERSITAET BREMEN
Country Germany
Call Details Advanced Grant (AdG), PE10, ERC-2014-ADG
Summary Lipid biomarkers provide unique information to disciplines such as paleoceanography, paleoecology and biogeochemistry. Factors limiting their scope include high sample demand and analytical complexity, constraining resolution of time and space to decadal and centimeter scales, respectively. However, dynamic interactions between physical, chemical and biological processes are recorded within sedimentary matrices at finer scales; lipid biomarkers could decode this sedimentary fine print if the limitations of resolution could be overcome. In a recent PNAS paper, we have demonstrated that this can be done and shown that µm-scale molecular images of paleoenvironmental and geobiological processes can be obtained directly on surfaces of cut sediment cores via laser desorption ionization coupled to mass spectrometry. The project ZOOMecular will build on this innovation by interrogating laminated sediment archives of Late Quaternary climate change and dissecting the complex environmental and ecological responses at subannual resolution. Through analysis of spatial associations of lipid biomarkers with the sedimentary matrix, we will provide a new view of the mechanisms underlying delivery to and preservation of molecular signals in sedimentary records. ZOOMecular will seek to examine the microbial habitat niches at sedimentary interfaces that are home to globally important biogeochemical processes but that are largely known from studies of cm3-scale samples. To enable these pioneering studies, we will develop innovative analytical protocols for a suite of informative biomarkers and for the acquisition of congruent molecular and elemental maps of geological samples. ZOOMecular will unlock otherwise inaccessible information of broad geoscientific relevance; its goals go far beyond the state-of-the-art and its outcome has the potential to transform biomarker research. Such a project can be successfully realized only within a frontier research scheme as provided by the ERC.
Summary
Lipid biomarkers provide unique information to disciplines such as paleoceanography, paleoecology and biogeochemistry. Factors limiting their scope include high sample demand and analytical complexity, constraining resolution of time and space to decadal and centimeter scales, respectively. However, dynamic interactions between physical, chemical and biological processes are recorded within sedimentary matrices at finer scales; lipid biomarkers could decode this sedimentary fine print if the limitations of resolution could be overcome. In a recent PNAS paper, we have demonstrated that this can be done and shown that µm-scale molecular images of paleoenvironmental and geobiological processes can be obtained directly on surfaces of cut sediment cores via laser desorption ionization coupled to mass spectrometry. The project ZOOMecular will build on this innovation by interrogating laminated sediment archives of Late Quaternary climate change and dissecting the complex environmental and ecological responses at subannual resolution. Through analysis of spatial associations of lipid biomarkers with the sedimentary matrix, we will provide a new view of the mechanisms underlying delivery to and preservation of molecular signals in sedimentary records. ZOOMecular will seek to examine the microbial habitat niches at sedimentary interfaces that are home to globally important biogeochemical processes but that are largely known from studies of cm3-scale samples. To enable these pioneering studies, we will develop innovative analytical protocols for a suite of informative biomarkers and for the acquisition of congruent molecular and elemental maps of geological samples. ZOOMecular will unlock otherwise inaccessible information of broad geoscientific relevance; its goals go far beyond the state-of-the-art and its outcome has the potential to transform biomarker research. Such a project can be successfully realized only within a frontier research scheme as provided by the ERC.
Max ERC Funding
3 000 000 €
Duration
Start date: 2015-11-01, End date: 2021-04-30
Project acronym ZooMWest
Project Zooarchaeology and Mobility in the Western Mediterranean: husbandry production from the Late Bronze Age to Late Antiquity
Researcher (PI) Silvia VALENZUELA LAMAS
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Country Spain
Call Details Starting Grant (StG), SH6, ERC-2016-STG
Summary Human survival and success is substantially determined by the ability to move across the landscape and adapt. Consequently, ‘mobility’ is a crucial topic in historical and archaeological research. To overcome the seasonal scarcity of food and the related over-grazing of pastures, it is essential for animal husbandry to move across territories. However, the decision to allow or deny rights of way to mobile people and livestock depends on political judgements. How might these shape animal husbandry production, and society?
The period between the Late Bronze Age and Late Antiquity in the Western Mediterranean witnessed the development of complex societies with a high territorial component, the Roman conquest, and the decline of the Western Roman Empire. Animal husbandry reflects human decisions regarding the management of resources, and the study of livestock rearing in specific geographical locations is possible through the isotopic analysis of ancient animal teeth. Consequently, we can analyse whether the nucleation of power occurring during the Bronze and Iron Ages, the centralization in Roman times and the later re-fragmentation in Late Antiquity transformed animal husbandry production. Crucially, we can then understand how political systems and decisions shaped human mobility through investigating animal production.
ZooMWest brings together isotopic chemistry, ancient DNA, zooarchaeology and geospatial analysis through four related work packages. Other than elucidating long term debates in archaeology –did transhumance exist in prehistoric Europe?–, this multidisciplinary and innovative project will create an open-access database of strontium and oxygen stable isotopes of the Iberian Peninsula and Italy. This database will enable us to refine geographic provenance to any discipline assessing the origin of matter, including geology, forensic studies, and the alimentary industry, as strontium and oxygen are present in many molecules, including organic tissues.
Summary
Human survival and success is substantially determined by the ability to move across the landscape and adapt. Consequently, ‘mobility’ is a crucial topic in historical and archaeological research. To overcome the seasonal scarcity of food and the related over-grazing of pastures, it is essential for animal husbandry to move across territories. However, the decision to allow or deny rights of way to mobile people and livestock depends on political judgements. How might these shape animal husbandry production, and society?
The period between the Late Bronze Age and Late Antiquity in the Western Mediterranean witnessed the development of complex societies with a high territorial component, the Roman conquest, and the decline of the Western Roman Empire. Animal husbandry reflects human decisions regarding the management of resources, and the study of livestock rearing in specific geographical locations is possible through the isotopic analysis of ancient animal teeth. Consequently, we can analyse whether the nucleation of power occurring during the Bronze and Iron Ages, the centralization in Roman times and the later re-fragmentation in Late Antiquity transformed animal husbandry production. Crucially, we can then understand how political systems and decisions shaped human mobility through investigating animal production.
ZooMWest brings together isotopic chemistry, ancient DNA, zooarchaeology and geospatial analysis through four related work packages. Other than elucidating long term debates in archaeology –did transhumance exist in prehistoric Europe?–, this multidisciplinary and innovative project will create an open-access database of strontium and oxygen stable isotopes of the Iberian Peninsula and Italy. This database will enable us to refine geographic provenance to any discipline assessing the origin of matter, including geology, forensic studies, and the alimentary industry, as strontium and oxygen are present in many molecules, including organic tissues.
Max ERC Funding
1 199 319 €
Duration
Start date: 2017-04-01, End date: 2022-01-31
Project acronym ZPR
Project The Pancreas Regulome: From causality to prediction of non-coding mutations in human pancreatic diseases
Researcher (PI) Jose Carlos Ribeiro Bessa
Host Institution (HI) INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR-IBMC
Country Portugal
Call Details Starting Grant (StG), LS2, ERC-2015-STG
Summary Several human pancreatic diseases have been characterized, being the diabetes the most common. Like others, this genetic disease is related to disrupted non-coding cis-regulatory elements (CREs) that culminate in altered gene expression. Although Genome Wide Association Studies support this hypothesis, it’s still unclear how mutations on CREs contribute to disease. The translation from the “non-coding code” to phenotype is an exciting and unexplored field that we will approach in this project with the help of the zebrafish as a suitable animal model. We aim to uncover the implications of the disruption of pancreas CREs and how they contribute to diabetes in vivo. For this we will study transcriptional regulation of genes in zebrafish. The similarities between zebrafish and mammal pancreas and the evolutionary conservation of pancreas transcription factors (TF) make it an excellent model to approach and study this disease. In this project we will characterize the zebrafish insulin producing beta-cell regulome, by determining the active CREs in this cell type and their bound TFs. Then we will compare this information with a similar dataset recently available for human beta-cells, to define functional orthologs in these species. Selected CREs will be tested by in vivo gene reporter assays in zebrafish, focusing on those functionally equivalent to human CREs where risk alleles have been associated with diabetes or those regulating genes involved in diabetes. Later these CREs will be mutated in the zebrafish genome to validate their contribution to diabetes. Finally we will translate this to predict new human disease-associated CREs by focusing on the regulatory landscape of diabetes-associated genes, without the need of having countless patients to uncover them. With this project we will create a model system that will allow the identification of new diabetes-associated CREs, which might have a great impact in clinical management of this epidemic disease.
Summary
Several human pancreatic diseases have been characterized, being the diabetes the most common. Like others, this genetic disease is related to disrupted non-coding cis-regulatory elements (CREs) that culminate in altered gene expression. Although Genome Wide Association Studies support this hypothesis, it’s still unclear how mutations on CREs contribute to disease. The translation from the “non-coding code” to phenotype is an exciting and unexplored field that we will approach in this project with the help of the zebrafish as a suitable animal model. We aim to uncover the implications of the disruption of pancreas CREs and how they contribute to diabetes in vivo. For this we will study transcriptional regulation of genes in zebrafish. The similarities between zebrafish and mammal pancreas and the evolutionary conservation of pancreas transcription factors (TF) make it an excellent model to approach and study this disease. In this project we will characterize the zebrafish insulin producing beta-cell regulome, by determining the active CREs in this cell type and their bound TFs. Then we will compare this information with a similar dataset recently available for human beta-cells, to define functional orthologs in these species. Selected CREs will be tested by in vivo gene reporter assays in zebrafish, focusing on those functionally equivalent to human CREs where risk alleles have been associated with diabetes or those regulating genes involved in diabetes. Later these CREs will be mutated in the zebrafish genome to validate their contribution to diabetes. Finally we will translate this to predict new human disease-associated CREs by focusing on the regulatory landscape of diabetes-associated genes, without the need of having countless patients to uncover them. With this project we will create a model system that will allow the identification of new diabetes-associated CREs, which might have a great impact in clinical management of this epidemic disease.
Max ERC Funding
1 497 520 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym ZSCAN
Project Hand pose and gesture analysis for next generation device interaction
Researcher (PI) Ron Kimmel
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Country Israel
Call Details Proof of Concept (PoC), PC1, ERC-2014-PoC
Summary A touch-less, markerless interface for next generation Virtual Reality headsets and laptops (with embedded 3D sensors expected early 2015), will be possible only when accurate and robust finger and hand pose detection is available and developers can easily build applications with these natural interfaces. Solutions based on color cameras are problematic because of the restrictions on environment lighting, complex backgrounds and varied skin tones. A recent breakthrough during research within our current ERC grant has been the development of a highly efficient prototype system that is capable of real-time markerless fingertip and hand pose detection and analysis using 3D sensors. Exposing this functionality for future human-computer interfaces is an important and necessary step forward that will allow more intuitive and effective interaction with next generation computing systems. Upscaling our current prototype system and packaging its functionality for easy use by developers is precisely the innovation we aim to implement in this PoC.
Summary
A touch-less, markerless interface for next generation Virtual Reality headsets and laptops (with embedded 3D sensors expected early 2015), will be possible only when accurate and robust finger and hand pose detection is available and developers can easily build applications with these natural interfaces. Solutions based on color cameras are problematic because of the restrictions on environment lighting, complex backgrounds and varied skin tones. A recent breakthrough during research within our current ERC grant has been the development of a highly efficient prototype system that is capable of real-time markerless fingertip and hand pose detection and analysis using 3D sensors. Exposing this functionality for future human-computer interfaces is an important and necessary step forward that will allow more intuitive and effective interaction with next generation computing systems. Upscaling our current prototype system and packaging its functionality for easy use by developers is precisely the innovation we aim to implement in this PoC.
Max ERC Funding
150 000 €
Duration
Start date: 2015-06-01, End date: 2016-11-30
Project acronym ZygoticFate
Project Zygotic Cell Fate and Parent-Biased Gene Expression in Fission Yeast
Researcher (PI) Aleksandar Vjestica
Host Institution (HI) UNIVERSITE DE LAUSANNE
Country Switzerland
Call Details Starting Grant (StG), LS3, ERC-2020-STG
Summary As two gametes fuse, the newly formed zygote immediately represses mating, to prevent polyploid formation, and triggers the developmental program that gives rise to a new individual. My work showed that zygotes of fission yeast and higher eukaryotes bare striking similarities, and here I propose to use this powerful model system to explore the basic mechanisms of gamete-to-zygote transition. Working in fission yeast, where gametes and zygotes are well-defined and accessible to outstanding plethora of experimental approaches, will show how different regulatory mechanisms synergize to execute this key cell fate switch.
Our first aim explores zygotic regulation of gene expression and mating blocks. First, to show how zygote-specific signaling propagates, we will identify its targets using biochemical screens. Second, we will analyse how zygotes alter gene expression. High-throughput sequencing will show transcriptional dynamics and genetics approaches will test its regulation and relevance. Third, we will combine microscopy and genetics to reveal the workings of fungal re-fertilization blocks.
Our second aim explores roles and regulation of the parent-biased allele expression in fungal zygotes that I recently discovered. While biochemical and sequencing-based screens will identify genes asymmetrically expressed from parental genomes, genetics strategies will test their roles. A structural biology workpackage will show how a simple homeodomain transcription factor drives the bias between parental genomes.
Similarities between zygotes of fission yeast and higher eukaryotes hint to the relevance of our work for other developmental systems. By understanding fungal blocks to re-fertilization, which have been previously completely overlooked, we may identify their conserved principles, as increasingly evident for other sexual processes. Finally, exploring the bias in expression of parental alleles in yeast may help explain its recurrence in distant plant and animal lineages.
Summary
As two gametes fuse, the newly formed zygote immediately represses mating, to prevent polyploid formation, and triggers the developmental program that gives rise to a new individual. My work showed that zygotes of fission yeast and higher eukaryotes bare striking similarities, and here I propose to use this powerful model system to explore the basic mechanisms of gamete-to-zygote transition. Working in fission yeast, where gametes and zygotes are well-defined and accessible to outstanding plethora of experimental approaches, will show how different regulatory mechanisms synergize to execute this key cell fate switch.
Our first aim explores zygotic regulation of gene expression and mating blocks. First, to show how zygote-specific signaling propagates, we will identify its targets using biochemical screens. Second, we will analyse how zygotes alter gene expression. High-throughput sequencing will show transcriptional dynamics and genetics approaches will test its regulation and relevance. Third, we will combine microscopy and genetics to reveal the workings of fungal re-fertilization blocks.
Our second aim explores roles and regulation of the parent-biased allele expression in fungal zygotes that I recently discovered. While biochemical and sequencing-based screens will identify genes asymmetrically expressed from parental genomes, genetics strategies will test their roles. A structural biology workpackage will show how a simple homeodomain transcription factor drives the bias between parental genomes.
Similarities between zygotes of fission yeast and higher eukaryotes hint to the relevance of our work for other developmental systems. By understanding fungal blocks to re-fertilization, which have been previously completely overlooked, we may identify their conserved principles, as increasingly evident for other sexual processes. Finally, exploring the bias in expression of parental alleles in yeast may help explain its recurrence in distant plant and animal lineages.
Max ERC Funding
1 702 705 €
Duration
Start date: 2020-12-01, End date: 2025-11-30
Project acronym µTHALYS
Project Micro-Technologies and Heterogeneous Advanced Platforms for Implantable Medical Systems
Researcher (PI) Robert M.O. Puers
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Country Belgium
Call Details Advanced Grant (AdG), PE8, ERC-2013-ADG
Summary The μTHALYS project aims to create a technology platform that enables a next revolution by bringing microsystem technology to the next level in terms of integration, miniaturization and multifunctionality and applying this development to address pending needs in health care.
Several breakthrough materials, basic concepts and fabrication techniques will be developed based on silicon or going far beyond silicon: At the wafer scale integration level, integration of advanced polymers (optics, conductive polymers, ionic polymer-metal composites) will be studied. These will be applied in several novel subminiature actuator and sensor devices with broad application potential, amongst which microfluidic systems, pressure sensing arrays,
In order to come to complex 3D systems combining modalities as optics, microfluidics, actuators and electronics, advanced device level fabrication and hybrid assembly technologies will be studied as well. Furthermore, the methods for packaging implants (flex/stretch interconnect technology, advanced interposers,…) will be pushed far beyond the current state of the art. The adoption of soft, and even
bioresorbable materials for packaging and interconnects will spectacularly improve the human-implant interface.
Another important research line pursued is the study of ultra-low power electronics for medical implants: sensor interfacing, A/D conversion, signal processing, data communication and power transfer.
These fundamental research activities will lead to many applied projects and valorization activities during and long afterwards the end of this grant. In the project itself, two main medical applications are targeted directly: a urinary pacemaker to prevent incontinence, and a new generation of implantable electrodes for neurology.
Summary
The μTHALYS project aims to create a technology platform that enables a next revolution by bringing microsystem technology to the next level in terms of integration, miniaturization and multifunctionality and applying this development to address pending needs in health care.
Several breakthrough materials, basic concepts and fabrication techniques will be developed based on silicon or going far beyond silicon: At the wafer scale integration level, integration of advanced polymers (optics, conductive polymers, ionic polymer-metal composites) will be studied. These will be applied in several novel subminiature actuator and sensor devices with broad application potential, amongst which microfluidic systems, pressure sensing arrays,
In order to come to complex 3D systems combining modalities as optics, microfluidics, actuators and electronics, advanced device level fabrication and hybrid assembly technologies will be studied as well. Furthermore, the methods for packaging implants (flex/stretch interconnect technology, advanced interposers,…) will be pushed far beyond the current state of the art. The adoption of soft, and even
bioresorbable materials for packaging and interconnects will spectacularly improve the human-implant interface.
Another important research line pursued is the study of ultra-low power electronics for medical implants: sensor interfacing, A/D conversion, signal processing, data communication and power transfer.
These fundamental research activities will lead to many applied projects and valorization activities during and long afterwards the end of this grant. In the project itself, two main medical applications are targeted directly: a urinary pacemaker to prevent incontinence, and a new generation of implantable electrodes for neurology.
Max ERC Funding
2 452 885 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
