Project acronym CONVEXVISION
Project Convex Optimization Methods for Computer Vision and Image Analysis
Researcher (PI) Daniel Cremers
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), PE6, ERC-2009-StG
Summary Optimization methods have become an established paradigm to address most Computer Vision challenges including the
reconstruction of three-dimensional objects from multiple images, or the tracking of a deformable shape over time. Yet, it has
been largely overlooked that optimization approaches are practically useless if they do not come with efficient algorithms to
compute minimizers of respective energies. Most existing formulations give rise to non-convex energies. As a consequence,
solutions highly depend on the choice of minimization scheme and implementational (initialization, time step sizes, etc.), with
little or no guarantees regarding the quality of computed solutions and their robustness to perturbations of the input data.
In the proposed research project, we plan to develop optimization methods for Computer Vision which allow to efficiently
compute globally optimal solutions. Preliminary results indicate that this will drastically leverage the power of optimization
methods and their applicability in a substantially broader context. Specifically we will focus on three lines of research: 1) We
will develop convex formulations for a variety of challenges. While convex formulations are currently being developed for
low-level problems such as image segmentation, our main effort will focus on carrying convex optimization to higher level
problems of image understanding and scene interpretation. 2) We will investigate alternative strategies of global optimization
by means of discrete graph theoretic methods. We will characterize advantages and drawbacks of continuous and discrete
methods and thereby develop novel algorithms combining the advantages of both approaches. 3) We will go beyond convex
formulations, developing relaxation schemes that compute near-optimal solutions for problems that cannot be expressed by
convex functionals.
Summary
Optimization methods have become an established paradigm to address most Computer Vision challenges including the
reconstruction of three-dimensional objects from multiple images, or the tracking of a deformable shape over time. Yet, it has
been largely overlooked that optimization approaches are practically useless if they do not come with efficient algorithms to
compute minimizers of respective energies. Most existing formulations give rise to non-convex energies. As a consequence,
solutions highly depend on the choice of minimization scheme and implementational (initialization, time step sizes, etc.), with
little or no guarantees regarding the quality of computed solutions and their robustness to perturbations of the input data.
In the proposed research project, we plan to develop optimization methods for Computer Vision which allow to efficiently
compute globally optimal solutions. Preliminary results indicate that this will drastically leverage the power of optimization
methods and their applicability in a substantially broader context. Specifically we will focus on three lines of research: 1) We
will develop convex formulations for a variety of challenges. While convex formulations are currently being developed for
low-level problems such as image segmentation, our main effort will focus on carrying convex optimization to higher level
problems of image understanding and scene interpretation. 2) We will investigate alternative strategies of global optimization
by means of discrete graph theoretic methods. We will characterize advantages and drawbacks of continuous and discrete
methods and thereby develop novel algorithms combining the advantages of both approaches. 3) We will go beyond convex
formulations, developing relaxation schemes that compute near-optimal solutions for problems that cannot be expressed by
convex functionals.
Max ERC Funding
1 985 400 €
Duration
Start date: 2010-09-01, End date: 2015-08-31
Project acronym END2ENDSECURITY
Project Practical design and analysis of certifiably secure protocols - theory and tools for end-to-end security
Researcher (PI) Michael Backes
Host Institution (HI) UNIVERSITAT DES SAARLANDES
Call Details Starting Grant (StG), PE6, ERC-2009-StG
Summary State-of-the-art technologies struggle to keep pace with possible security vulnerabilities. The lack of a consistent methodology and tools for analyzing security protocols throughout the various stages of their design hinders the detection and prevention of vulnerabilities and comprehensive protocol analysis. Moreover, state-of-the-art verification tools typically only address particular narrow aspects of a protocol's security and require expert knowledge; hence they do not help protocol designers. The challenge is to guarantee end-to-end security - from high-level specifications of the desired security requirements, to a specification of a security protocol that relies on innovative cryptographic primitives, to a secure, executable program. This proposal addresses key steps of this challenge: our goal is to develop a general methodology for automatically devising security protocols and programs based on high-level specifications of selected security requirements and protocol tasks. This includes developing a user-friendly interface for specifying the protocol's intended behavior and high-level security requirements, devising suitable abstract protocols, selecting suitable cryptographic instantiations, and generating a secure, streamlined implementation. This methodology will also include novel verification techniques that complement all design phases along with a theory which propagates verification results from phase to phase with the ultimate goal of certified end-to-end security. This includes developing type systems for analyzing abstract protocols, a general framework for conducting cryptographic proofs, and techniques for reasoning about executable code. The tools we develop should be automated and usable by non-experts.
Summary
State-of-the-art technologies struggle to keep pace with possible security vulnerabilities. The lack of a consistent methodology and tools for analyzing security protocols throughout the various stages of their design hinders the detection and prevention of vulnerabilities and comprehensive protocol analysis. Moreover, state-of-the-art verification tools typically only address particular narrow aspects of a protocol's security and require expert knowledge; hence they do not help protocol designers. The challenge is to guarantee end-to-end security - from high-level specifications of the desired security requirements, to a specification of a security protocol that relies on innovative cryptographic primitives, to a secure, executable program. This proposal addresses key steps of this challenge: our goal is to develop a general methodology for automatically devising security protocols and programs based on high-level specifications of selected security requirements and protocol tasks. This includes developing a user-friendly interface for specifying the protocol's intended behavior and high-level security requirements, devising suitable abstract protocols, selecting suitable cryptographic instantiations, and generating a secure, streamlined implementation. This methodology will also include novel verification techniques that complement all design phases along with a theory which propagates verification results from phase to phase with the ultimate goal of certified end-to-end security. This includes developing type systems for analyzing abstract protocols, a general framework for conducting cryptographic proofs, and techniques for reasoning about executable code. The tools we develop should be automated and usable by non-experts.
Max ERC Funding
1 074 807 €
Duration
Start date: 2010-02-01, End date: 2013-10-31
Project acronym ETHIO-SPARE
Project Cultural Heritage of Christian Ethiopia: Salvation, Preservation and Research
Researcher (PI) Denis Nosnitsin
Host Institution (HI) UNIVERSITAET HAMBURG
Call Details Starting Grant (StG), SH5, ERC-2009-StG
Summary Ethiopia is one of the countries with the most ancient Christian history, and the only country in Africa where Christianity became official religion as early as in the 4th century A.D. It is also the only country in the region where the history has been documented in written sources: manuscripts in possession of ca. 600 monasteries and 20,000 churches, some of which date back to early Middle Ages, have been estimated to number up to ca. 200,000. Only a minor part of these archives have so far received scholarly evaluation, only less than one tenth of manuscripts have been microfilmed or digitalized, and only those that have come in possession of European libraries have been duly catalogued and are well protected. A great part of this unique heritage is on the verge of extinction, and urgent action needs to be taken to save it from complete disappearance. A thorough research into the texts will grant insight into the mentality of this African region and provide parallels to the ways other African regions without ancient written tradition may have developed, as well as to the ways Christianity spread in medieval Europe: in monastic Ethiopia some features now lost in the civilized world may still be observed. The project will unite scholars working in the fields of philology, codicology, digital philology, religious studies, anthropology, art history, and book preservation, who will secure the most important pieces of historical written evidence and carry out first-hand in-depth research into the witnesses. Local history and oral traditions collected during field research will allow a comprehensive and complete evaluation of the sources. Focus on historiographic and legal documents will allow a detailed reconstruction of local history of selected regions.
Summary
Ethiopia is one of the countries with the most ancient Christian history, and the only country in Africa where Christianity became official religion as early as in the 4th century A.D. It is also the only country in the region where the history has been documented in written sources: manuscripts in possession of ca. 600 monasteries and 20,000 churches, some of which date back to early Middle Ages, have been estimated to number up to ca. 200,000. Only a minor part of these archives have so far received scholarly evaluation, only less than one tenth of manuscripts have been microfilmed or digitalized, and only those that have come in possession of European libraries have been duly catalogued and are well protected. A great part of this unique heritage is on the verge of extinction, and urgent action needs to be taken to save it from complete disappearance. A thorough research into the texts will grant insight into the mentality of this African region and provide parallels to the ways other African regions without ancient written tradition may have developed, as well as to the ways Christianity spread in medieval Europe: in monastic Ethiopia some features now lost in the civilized world may still be observed. The project will unite scholars working in the fields of philology, codicology, digital philology, religious studies, anthropology, art history, and book preservation, who will secure the most important pieces of historical written evidence and carry out first-hand in-depth research into the witnesses. Local history and oral traditions collected during field research will allow a comprehensive and complete evaluation of the sources. Focus on historiographic and legal documents will allow a detailed reconstruction of local history of selected regions.
Max ERC Funding
1 746 080 €
Duration
Start date: 2009-12-01, End date: 2015-05-31
Project acronym JEWCOM
Project History of European -Jewish Communication in the 20th Century
Researcher (PI) Bettina Von Jagow
Host Institution (HI) UNIVERSITAT ERFURT
Call Details Starting Grant (StG), SH5, ERC-2009-StG
Summary The project focuses on European - Jewish communication about political and socio-historical events as well as on private discussions. 10 significant correspondences written by German speaking Jewish authors in the 20th century travelling through Europe, Palestine/Israel and to the US, will be analysed to examine how an individual memory as part of the cultural area Europe is shaped. The aim of the project is to examine the interferences of individual and cultural memory in order to show that cultural memory is mainly structured through individual perception. Prof. von Jagow proposes that beyond traditions of describing cultural memory in a historic way the analyses of the letters can widen the perspective because letters as ego-documents are a medium of private and public discussion. Although it is unconventional to analyse a history of European-Jewish communication on the basis of letters, it is evident that these sources open completely new horizons on cultural memory by a theoretical approach beyond the state-of-the art which stems from transdisciplinary methodology. It is grounded in the fact that literary documents are of highest cultural and anthropological value. The project is centered in a highly advanced theoretical approach of history from below centered in emphasizing subjectivity. Works of art are of extraordinary value taking into consideration that they are both: a seismographic code of political and socio-historical reflections and a personal and aesthetic perspective upon. As an another companion of Jewish writing and thought, a history from below emphasizes on subjectivity and perception in order to enlarge the European-Jewish memory in a completely new approach to cultural remembering. This approach is of general interest not only in literary critics, but also in other disciplines like in history, history of science and medicine and ethics.
Summary
The project focuses on European - Jewish communication about political and socio-historical events as well as on private discussions. 10 significant correspondences written by German speaking Jewish authors in the 20th century travelling through Europe, Palestine/Israel and to the US, will be analysed to examine how an individual memory as part of the cultural area Europe is shaped. The aim of the project is to examine the interferences of individual and cultural memory in order to show that cultural memory is mainly structured through individual perception. Prof. von Jagow proposes that beyond traditions of describing cultural memory in a historic way the analyses of the letters can widen the perspective because letters as ego-documents are a medium of private and public discussion. Although it is unconventional to analyse a history of European-Jewish communication on the basis of letters, it is evident that these sources open completely new horizons on cultural memory by a theoretical approach beyond the state-of-the art which stems from transdisciplinary methodology. It is grounded in the fact that literary documents are of highest cultural and anthropological value. The project is centered in a highly advanced theoretical approach of history from below centered in emphasizing subjectivity. Works of art are of extraordinary value taking into consideration that they are both: a seismographic code of political and socio-historical reflections and a personal and aesthetic perspective upon. As an another companion of Jewish writing and thought, a history from below emphasizes on subjectivity and perception in order to enlarge the European-Jewish memory in a completely new approach to cultural remembering. This approach is of general interest not only in literary critics, but also in other disciplines like in history, history of science and medicine and ethics.
Max ERC Funding
600 000 €
Duration
Start date: 2010-02-01, End date: 2015-01-31
Project acronym JTOMO
Project Study of the molecular organization of cell junctions by cryo-electron tomography
Researcher (PI) Achilleas Frangakis
Host Institution (HI) JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN
Call Details Starting Grant (StG), LS1, ERC-2009-StG
Summary Cells sense, affect and respond to their environment through the fundamental function of adhesion. Several types of adhesion sites, which are mediated via dynamically maintained multi-protein structures, anchor extracellular-matrix proteins to the cytoskeleton. Despite considerable efforts, the long-standing questions of how adhesion sites are formed, structured and regulated remain unanswered. In this research plan we will investigate desmosomes and adherens junctions by cryo-electron tomography of cells and tissue. The principal objectives are: (a) to visualize the molecular architecture and reveal the structural differences of the adhesion sites under various conditions and influences, i.e. mutations, wounds, etc. (b) to reveal their molecular association to the cytoskeleton (intermediate and actin filaments respectively), and to chart the network of interactions underlying cellular adhesion, and (c) to develop novel pattern recognition and classification techniques in order to structurally characterize the adhesion sites in toto by cryo-electron tomography of vitreous sections. We will use pattern recognition techniques and locally averaged cryo-electron sub-tomograms to quantify the macromolecular complexes in terms of stoichiometry and protein interactions in situ at high resolution (~3 nm). In particular, we aim to reveal how a pool of constituent proteins is organized in the two adhesion sites. Significant amounts of information coming from immunogold electron microscopy, fragments from X-ray structures, force measurements with atomic force microscopy, and structural bioinformatics will be integrated into our cryo-electron tomograms. This research will pioneer structural comparisons of protein networks at nanometer resolution in situ and in toto. The experimental and theoretical methods that will be developed would be indispensable for studying any spatially constrained protein network whose state depends on local properties.
Summary
Cells sense, affect and respond to their environment through the fundamental function of adhesion. Several types of adhesion sites, which are mediated via dynamically maintained multi-protein structures, anchor extracellular-matrix proteins to the cytoskeleton. Despite considerable efforts, the long-standing questions of how adhesion sites are formed, structured and regulated remain unanswered. In this research plan we will investigate desmosomes and adherens junctions by cryo-electron tomography of cells and tissue. The principal objectives are: (a) to visualize the molecular architecture and reveal the structural differences of the adhesion sites under various conditions and influences, i.e. mutations, wounds, etc. (b) to reveal their molecular association to the cytoskeleton (intermediate and actin filaments respectively), and to chart the network of interactions underlying cellular adhesion, and (c) to develop novel pattern recognition and classification techniques in order to structurally characterize the adhesion sites in toto by cryo-electron tomography of vitreous sections. We will use pattern recognition techniques and locally averaged cryo-electron sub-tomograms to quantify the macromolecular complexes in terms of stoichiometry and protein interactions in situ at high resolution (~3 nm). In particular, we aim to reveal how a pool of constituent proteins is organized in the two adhesion sites. Significant amounts of information coming from immunogold electron microscopy, fragments from X-ray structures, force measurements with atomic force microscopy, and structural bioinformatics will be integrated into our cryo-electron tomograms. This research will pioneer structural comparisons of protein networks at nanometer resolution in situ and in toto. The experimental and theoretical methods that will be developed would be indispensable for studying any spatially constrained protein network whose state depends on local properties.
Max ERC Funding
1 724 400 €
Duration
Start date: 2010-01-01, End date: 2015-12-31
Project acronym NEDD8ANDCRLLIGASES
Project Regulation and Function of Cullin-Ring E3 ubiquitin ligases and the Nedd8 ubiquitin-like protein modification system
Researcher (PI) Thimo Kasimir Kurz
Host Institution (HI) UNIVERSITY OF DUNDEE
Call Details Starting Grant (StG), LS1, ERC-2009-StG
Summary Cullin-RING E3 ubiquitin ligases (CRLs) are multi-subunit enzyme complexes that catalyze isopeptide bond formation between the C-terminal glycine residue of the small protein ubiquitin and lysine residues of substrate proteins (ubiquitination). Multiple rounds of ubiquitination lead to the formation of ubiquitin chains, which are recognized by the 26S-proteasome, a protease that degrades the substrates. Targeted protein degradation by CRLs is an important part of many essential cellular processes. Progression of the cell cycle, for example, requires CRL-dependent ubiquitination and degradation of cyclin-dependent kinase inhibitors (CKIs). Clearly, substrate ubiquitination needs to occur at the right time and place, and it is thus essential that CRL activity is tightly regulated. In fact, the malfunction of CRLs has been associated with many human diseases, including cancer. One mode of CRL regulation is the activation of the ligase by the small ubiquitin-like molecule Nedd8 (neddylation). Neddylation of the cullin triggers the formation of an active ligase complex and induces structural changes that allow efficient substrate ubiquitination. My proposal aims at gaining mechanistic insights into the activation and inactivation cycles of CRL complexes. I propose to study the regulation of cullin neddylation and the role of the newly identified Nedd8 E3 ligase Dcn1 in this process. I will identify new substrates of the Nedd8 pathway with yeast genetics and biochemistry and generate a systems-wide map of genetic interactions with CRL substrates and regulators using synthetic genetic array (SGA) analysis.
Summary
Cullin-RING E3 ubiquitin ligases (CRLs) are multi-subunit enzyme complexes that catalyze isopeptide bond formation between the C-terminal glycine residue of the small protein ubiquitin and lysine residues of substrate proteins (ubiquitination). Multiple rounds of ubiquitination lead to the formation of ubiquitin chains, which are recognized by the 26S-proteasome, a protease that degrades the substrates. Targeted protein degradation by CRLs is an important part of many essential cellular processes. Progression of the cell cycle, for example, requires CRL-dependent ubiquitination and degradation of cyclin-dependent kinase inhibitors (CKIs). Clearly, substrate ubiquitination needs to occur at the right time and place, and it is thus essential that CRL activity is tightly regulated. In fact, the malfunction of CRLs has been associated with many human diseases, including cancer. One mode of CRL regulation is the activation of the ligase by the small ubiquitin-like molecule Nedd8 (neddylation). Neddylation of the cullin triggers the formation of an active ligase complex and induces structural changes that allow efficient substrate ubiquitination. My proposal aims at gaining mechanistic insights into the activation and inactivation cycles of CRL complexes. I propose to study the regulation of cullin neddylation and the role of the newly identified Nedd8 E3 ligase Dcn1 in this process. I will identify new substrates of the Nedd8 pathway with yeast genetics and biochemistry and generate a systems-wide map of genetic interactions with CRL substrates and regulators using synthetic genetic array (SGA) analysis.
Max ERC Funding
1 397 677 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
Project acronym NOT
Project Narratives of Terror and Disappearance. Fantastic Dimensions of Argentina' s Collective Memory since the Military Dictatorship
Researcher (PI) Kirsten Mahlke
Host Institution (HI) UNIVERSITAT KONSTANZ
Call Details Starting Grant (StG), SH5, ERC-2009-StG
Summary Terror and its social and cultural effects are the most unspeakable and traumatic facts of the 20th and 21st centuries. The two-fold argument is that terror a) operates and perpetuates itself by means of fantastic narratives, and b) is one of the characteristic elements evoked by the fantastic genre. This project seeks to investigate the interdependency of fantastic narrative and the historical phenomenon of terror. The five-year, six-member project combines a literary theoretical reassessment of the fantastic as a mode of telling the unspeakable with a historical case study of the Argentinean 'war on terrorism' during the military dictatorship of 1976-83 and its aftermath. The discourses of actual terror and imaginary fantastic intersect in the figure of the Disappeared: those suspected of terrorist activities against the state were systematically abducted, tortured, murdered, and forced to disappear. The Disappeared are not merely missing subjects, but also a social cipher of indeterminacy that decisively organizes traumatic past and political present through narrative. This project uses an approach which combines narratological analysis with a Cultural Studies perspective including Political Science and Social Anthropology to investigate the specific ways that the figure of the Disappeared shapes the Argentinean social body, its histories and collective self-understanding. For the first time, the Disappeared are analyzed as integral figures of the transition between historical reality and fantastical imagination. Their case history represents a paradigm for a terroristic answer to terrorism and can shed light on current debates on the war on terrorism . The research group will enquire into the conditions of emergence, authorships, paths of dissemination, the semantic de-and re-codings and reciprocal relations of concepts of terror, security and subversion. The methodology therefore combines qualitative Cultural Studies with quantitative analyses.
Summary
Terror and its social and cultural effects are the most unspeakable and traumatic facts of the 20th and 21st centuries. The two-fold argument is that terror a) operates and perpetuates itself by means of fantastic narratives, and b) is one of the characteristic elements evoked by the fantastic genre. This project seeks to investigate the interdependency of fantastic narrative and the historical phenomenon of terror. The five-year, six-member project combines a literary theoretical reassessment of the fantastic as a mode of telling the unspeakable with a historical case study of the Argentinean 'war on terrorism' during the military dictatorship of 1976-83 and its aftermath. The discourses of actual terror and imaginary fantastic intersect in the figure of the Disappeared: those suspected of terrorist activities against the state were systematically abducted, tortured, murdered, and forced to disappear. The Disappeared are not merely missing subjects, but also a social cipher of indeterminacy that decisively organizes traumatic past and political present through narrative. This project uses an approach which combines narratological analysis with a Cultural Studies perspective including Political Science and Social Anthropology to investigate the specific ways that the figure of the Disappeared shapes the Argentinean social body, its histories and collective self-understanding. For the first time, the Disappeared are analyzed as integral figures of the transition between historical reality and fantastical imagination. Their case history represents a paradigm for a terroristic answer to terrorism and can shed light on current debates on the war on terrorism . The research group will enquire into the conditions of emergence, authorships, paths of dissemination, the semantic de-and re-codings and reciprocal relations of concepts of terror, security and subversion. The methodology therefore combines qualitative Cultural Studies with quantitative analyses.
Max ERC Funding
1 200 000 €
Duration
Start date: 2010-04-01, End date: 2015-03-31
Project acronym REMODELLING
Project ATP dependent nucleosome remodelling - Single molecule studies and super-resolution microscopy
Researcher (PI) Jens Michaelis
Host Institution (HI) UNIVERSITAET ULM
Call Details Starting Grant (StG), LS1, ERC-2009-StG
Summary In eukaryotic cells the DNA is packaged into nucleosomes and higher order structures which lead to a condensation and protection of the DNA. During important cellular processes such as transcription or replication access to the DNA has to be granted. This is facilitated by ATP dependent nucleosome remodelling. The mechanistic details how the involved remodelling complexes succeed in providing access to the nucleosomal DNA are currently in spite of large experimental efforts not well understood. The aim of the proposal is to unravel the molecular mechanism of nucleosome remodelling using single-molecule fluorescence resonance energy transfer (FRET). By putting labels on the nucleosomal DNA, the histones or the remodellers we will - step by step - determine the conformational changes that occur during remodelling and use this information to build a mechanistic model. We will also use the controlled assembly of 30 nm fibers from purified components in order to determine how remodelling occurs in this structurally restricted environment. The large size of the chromatin fibers will dictate that in addition to FRET measurements, which will again be used to investigate local motion, super-resolution microscopy need to be employed to obtain information about long-distance movements. To this end we will use stochastic optical reconstruction microscopy (STORM), which allows for accuracy below 10 nm, thus ideally complementing the FRET approach. In summary our experiments will lead us to a mechanistic understanding of ATP dependent nucleosome remodelling, both on mono-nucleosomes as well as in higher order structures. This knowledge will in return stimulate new initiatives aimed at understanding the nature and regulation of chromatin dynamics in vivo.
Summary
In eukaryotic cells the DNA is packaged into nucleosomes and higher order structures which lead to a condensation and protection of the DNA. During important cellular processes such as transcription or replication access to the DNA has to be granted. This is facilitated by ATP dependent nucleosome remodelling. The mechanistic details how the involved remodelling complexes succeed in providing access to the nucleosomal DNA are currently in spite of large experimental efforts not well understood. The aim of the proposal is to unravel the molecular mechanism of nucleosome remodelling using single-molecule fluorescence resonance energy transfer (FRET). By putting labels on the nucleosomal DNA, the histones or the remodellers we will - step by step - determine the conformational changes that occur during remodelling and use this information to build a mechanistic model. We will also use the controlled assembly of 30 nm fibers from purified components in order to determine how remodelling occurs in this structurally restricted environment. The large size of the chromatin fibers will dictate that in addition to FRET measurements, which will again be used to investigate local motion, super-resolution microscopy need to be employed to obtain information about long-distance movements. To this end we will use stochastic optical reconstruction microscopy (STORM), which allows for accuracy below 10 nm, thus ideally complementing the FRET approach. In summary our experiments will lead us to a mechanistic understanding of ATP dependent nucleosome remodelling, both on mono-nucleosomes as well as in higher order structures. This knowledge will in return stimulate new initiatives aimed at understanding the nature and regulation of chromatin dynamics in vivo.
Max ERC Funding
1 395 381 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
Project acronym SRNAS
Project Small non-coding RNAs in cell function and disease
Researcher (PI) Gunter Meister
Host Institution (HI) UNIVERSITAET REGENSBURG
Call Details Starting Grant (StG), LS1, ERC-2009-StG
Summary Small non-coding RNAs including microRNAs (miRNAs), short interfering RNAs (siRNAs) or Piwi interacting RNAs (piRNAs) have been discovered recently and extensive research revealed that such RNAs function as key-regulators of gene expression. Small non-coding RNAs cooperate with members of the Argonaute (Ago) protein family to regulate gene expression at the level of transcription, mRNA stability or translation. While small RNAs serve as sequence-specific guides, Ago proteins constitute the mediators of gene silencing processes. In order to identify functional classes of small non-coding RNAs, it is important to analyze interactions with members of the Ago protein family. We propose to isolate and clone Ago-associated small RNAs. Processing products of small nucleolar RNAs (snoRNAs) can give rise to functional small RNAs and it is very likely that other non-coding RNAs including tRNAs or rRNAs produce functional small RNAs with so far unrecognized cellular functions. In the second part of the proposal we plan to investigate the role of miRNAs in disease. In the cancer field, the cancer stem cell hypothesis suggests the existence of tumor stem cells that are important for tumor maintenance. Such stem cells are difficult to target and might be the cause of tumor re-appearance after therapy. Since glioblastoma is a fatal tumor and tumor stem cells can be isolated we will analyze miRNA expression in glioblastoma stem cells. Indeed, a first cloning approach identified several tumor stem cell specific miRNAs. In the proposed project we plan to analyze the biological function of such glioblastoma stem cell-specific miRNAs. We hope that our work not only contributes to a better understanding of the cancer stem cell hypothesis but will also depict new ways for cancer therapy.
Summary
Small non-coding RNAs including microRNAs (miRNAs), short interfering RNAs (siRNAs) or Piwi interacting RNAs (piRNAs) have been discovered recently and extensive research revealed that such RNAs function as key-regulators of gene expression. Small non-coding RNAs cooperate with members of the Argonaute (Ago) protein family to regulate gene expression at the level of transcription, mRNA stability or translation. While small RNAs serve as sequence-specific guides, Ago proteins constitute the mediators of gene silencing processes. In order to identify functional classes of small non-coding RNAs, it is important to analyze interactions with members of the Ago protein family. We propose to isolate and clone Ago-associated small RNAs. Processing products of small nucleolar RNAs (snoRNAs) can give rise to functional small RNAs and it is very likely that other non-coding RNAs including tRNAs or rRNAs produce functional small RNAs with so far unrecognized cellular functions. In the second part of the proposal we plan to investigate the role of miRNAs in disease. In the cancer field, the cancer stem cell hypothesis suggests the existence of tumor stem cells that are important for tumor maintenance. Such stem cells are difficult to target and might be the cause of tumor re-appearance after therapy. Since glioblastoma is a fatal tumor and tumor stem cells can be isolated we will analyze miRNA expression in glioblastoma stem cells. Indeed, a first cloning approach identified several tumor stem cell specific miRNAs. In the proposed project we plan to analyze the biological function of such glioblastoma stem cell-specific miRNAs. We hope that our work not only contributes to a better understanding of the cancer stem cell hypothesis but will also depict new ways for cancer therapy.
Max ERC Funding
1 139 998 €
Duration
Start date: 2010-01-01, End date: 2014-12-31
