Project acronym miRLIFE
Project Molecular Characterization of the microRNA Life-Cycle
Researcher (PI) Stefan Ludwig Ameres
Host Institution (HI) INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH
Call Details Starting Grant (StG), LS1, ERC-2013-StG
Summary Small silencing RNAs regulate gene expression in nearly all eukaryotes and have enormous biotechnological and therapeutic potential. MicroRNAs belong to the larges family of trans-acting gene regulatory molecules in multicellular organisms. In flies and mammals, they control more than half of the protein-coding transcriptome, and act as key regulators of organismal development, physiology, and disease.
Here, we propose to study the molecular mechanisms that regulate microRNA homeostasis. We aim to understand how distinct small RNA profiles are established and maintained to coordinate the expression of more than half of all protein coding genes in flies and mammals. Our studies will provide insight into the processes that regulate the function of miRNAs, determine possible causes for aberrant miRNA levels, that have been associated with human diseases, and provide guidelines how to efficiently inhibit miRNA function for analytical and therapeutic purposes.
We aim to identify and characterize the molecular determinants of microRNA stability, to dissect the pathways that promote the sequence-specific degradation of microRNAs, and to understand the biological consequences and therapeutic potential of small RNA decay. We will develop novel tools to obtain a view on the intracellular dynamics of RNA silencing pathways, in order to determine the molecular features associated with small RNA biogenesis and decay.
Because of its genetic and biochemical tools, we will use Drosophila melanogaster as a model organism. We will employ a combination of bioinformatics, cell-free biochemical experiments, cell culture methods, and in vivo genetics. What we learn in flies we will test in vitro in mammalian cell extracts, in cultured human cell lines and in vivo in mice to identify where these processes are conserved and where they diverge.
Overall, our goal is to determine fundamental biological mechanisms of RNA silencing, a phenomenon with enormous biological and biomedical impact.
Summary
Small silencing RNAs regulate gene expression in nearly all eukaryotes and have enormous biotechnological and therapeutic potential. MicroRNAs belong to the larges family of trans-acting gene regulatory molecules in multicellular organisms. In flies and mammals, they control more than half of the protein-coding transcriptome, and act as key regulators of organismal development, physiology, and disease.
Here, we propose to study the molecular mechanisms that regulate microRNA homeostasis. We aim to understand how distinct small RNA profiles are established and maintained to coordinate the expression of more than half of all protein coding genes in flies and mammals. Our studies will provide insight into the processes that regulate the function of miRNAs, determine possible causes for aberrant miRNA levels, that have been associated with human diseases, and provide guidelines how to efficiently inhibit miRNA function for analytical and therapeutic purposes.
We aim to identify and characterize the molecular determinants of microRNA stability, to dissect the pathways that promote the sequence-specific degradation of microRNAs, and to understand the biological consequences and therapeutic potential of small RNA decay. We will develop novel tools to obtain a view on the intracellular dynamics of RNA silencing pathways, in order to determine the molecular features associated with small RNA biogenesis and decay.
Because of its genetic and biochemical tools, we will use Drosophila melanogaster as a model organism. We will employ a combination of bioinformatics, cell-free biochemical experiments, cell culture methods, and in vivo genetics. What we learn in flies we will test in vitro in mammalian cell extracts, in cultured human cell lines and in vivo in mice to identify where these processes are conserved and where they diverge.
Overall, our goal is to determine fundamental biological mechanisms of RNA silencing, a phenomenon with enormous biological and biomedical impact.
Max ERC Funding
1 499 631 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym mirspecificity
Project Spatio-temporal specificity of miRNA function
Researcher (PI) Maria Luisa Cochella
Host Institution (HI) FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH
Call Details Starting Grant (StG), LS1, ERC-2013-StG
Summary MicroRNAs are versatile regulators of gene expression and as such, they are essential parts of the gene regulatory networks controlling development and physiology of animals and plants. In particular, a number of miRNAs have been implicated in cell-type differentiation. Adding miRNAs to existing networks in particular subsets of cells can increase the complexity of developmental programs, and thus contribute to the vast diversity of cell types found in complex multicellular organisms.
In order to achieve this function, miRNAs have very diverse and highly specific spatio-temporal patterns of expression. Understanding, when and where miRNAs are expressed and how their expression is regulated is essential to place them in the correct cellular context and grasp their contribution to normal development and disease.
miRNA expression can be regulated at the transcriptional and post-transcriptional levels. While transcriptional regulation is known to generate distinct patterns of miRNA production, the contribution of post-transcriptional regulation of miRNA biogenesis and function to their spatio-temporal specificity is virtually unexplored. A few RNA binding proteins have been shown to affect miRNA biogenesis mostly in cell culture yet with one exception, none have been studied in the context of a whole developing organism where their roles in providing specificity to miRNA function could be assessed. Furthermore, only a handful of miRNAs are known to be post-transcriptionally regulated in tissue or stage-specific manners, mostly in organisms not amenable to genetic analysis, thus making it difficult to identify the underlying mechanisms.
I propose to use the genetic model system C. elegans to bridge these two stunted approaches. We will identify post-transcriptional regulators of miRNA biogenesis and activity and dissect their contribution to generating specific spatio-temporal domains of miRNA function and in doing so, increasing cell-type diversity.
Summary
MicroRNAs are versatile regulators of gene expression and as such, they are essential parts of the gene regulatory networks controlling development and physiology of animals and plants. In particular, a number of miRNAs have been implicated in cell-type differentiation. Adding miRNAs to existing networks in particular subsets of cells can increase the complexity of developmental programs, and thus contribute to the vast diversity of cell types found in complex multicellular organisms.
In order to achieve this function, miRNAs have very diverse and highly specific spatio-temporal patterns of expression. Understanding, when and where miRNAs are expressed and how their expression is regulated is essential to place them in the correct cellular context and grasp their contribution to normal development and disease.
miRNA expression can be regulated at the transcriptional and post-transcriptional levels. While transcriptional regulation is known to generate distinct patterns of miRNA production, the contribution of post-transcriptional regulation of miRNA biogenesis and function to their spatio-temporal specificity is virtually unexplored. A few RNA binding proteins have been shown to affect miRNA biogenesis mostly in cell culture yet with one exception, none have been studied in the context of a whole developing organism where their roles in providing specificity to miRNA function could be assessed. Furthermore, only a handful of miRNAs are known to be post-transcriptionally regulated in tissue or stage-specific manners, mostly in organisms not amenable to genetic analysis, thus making it difficult to identify the underlying mechanisms.
I propose to use the genetic model system C. elegans to bridge these two stunted approaches. We will identify post-transcriptional regulators of miRNA biogenesis and activity and dissect their contribution to generating specific spatio-temporal domains of miRNA function and in doing so, increasing cell-type diversity.
Max ERC Funding
1 499 458 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym SPAJORANA
Project Towards spin qubits and Majorana fermions in Germanium self-assembled hut-wires
Researcher (PI) Georgios Katsaros
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Starting Grant (StG), PE3, ERC-2013-StG
Summary A renewed interest in Ge has been sparked by the prospects of exploiting its lower effective mass and higher hole mobility to improve the performance of transistors. Ge emerges also as a promising material in the field of spin qubits, as its coherence times are expected to be very long. Finally, it has been proposed that strained Ge nanowires show an unusually large spin orbit interaction, making them thus suitable for the realization of Majorana fermions. In view of these facts, one is able to envision a new era of Ge in information technology.
The growth of Ge nanocrystals on Si was reported for the first time in 1990. This created great expectations that such structures could provide a valid route towards innovative, scalable and CMOS-compatible nanodevices. Two decades later the PI was able to realize the first devices based on such structures. His results show that Ge self-assembled quantum dots display a unique combination of electronic properties, i.e. low hyperfine interaction, strong and tunable spin-orbit coupling and spin selective tunneling. In 2012, the PI’s group went a step further and realized for the first time Ge nanowires monolithically integrated on Si substrates, which will allow the PI to move towards double quantum dots and Majorana fermions. In view of their exceptionally small cross section, these Ge wires hold promise for the realization of hole systems with exotic properties.
Within this project, these new wires will be investigated, both as spin as well as topological qubits. The objective of the present proposal is mainly to: a) study spin-injection by means of normal and superconducting contacts, b) study the characteristic time scales for spin dynamics and move towards electrical spin manipulation of holes, c) observe Majorana fermions in a p-type system. The PI’s vision is to couple spin and topological qubits in one “technological platform” enabling thus the coherent transfer of quantum information between them.
Summary
A renewed interest in Ge has been sparked by the prospects of exploiting its lower effective mass and higher hole mobility to improve the performance of transistors. Ge emerges also as a promising material in the field of spin qubits, as its coherence times are expected to be very long. Finally, it has been proposed that strained Ge nanowires show an unusually large spin orbit interaction, making them thus suitable for the realization of Majorana fermions. In view of these facts, one is able to envision a new era of Ge in information technology.
The growth of Ge nanocrystals on Si was reported for the first time in 1990. This created great expectations that such structures could provide a valid route towards innovative, scalable and CMOS-compatible nanodevices. Two decades later the PI was able to realize the first devices based on such structures. His results show that Ge self-assembled quantum dots display a unique combination of electronic properties, i.e. low hyperfine interaction, strong and tunable spin-orbit coupling and spin selective tunneling. In 2012, the PI’s group went a step further and realized for the first time Ge nanowires monolithically integrated on Si substrates, which will allow the PI to move towards double quantum dots and Majorana fermions. In view of their exceptionally small cross section, these Ge wires hold promise for the realization of hole systems with exotic properties.
Within this project, these new wires will be investigated, both as spin as well as topological qubits. The objective of the present proposal is mainly to: a) study spin-injection by means of normal and superconducting contacts, b) study the characteristic time scales for spin dynamics and move towards electrical spin manipulation of holes, c) observe Majorana fermions in a p-type system. The PI’s vision is to couple spin and topological qubits in one “technological platform” enabling thus the coherent transfer of quantum information between them.
Max ERC Funding
1 675 020 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
