Project acronym 3FLEX
Project Three-Component Fermi Gas Lattice Experiment
Researcher (PI) Selim Jochim
Host Institution (HI) RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Call Details Starting Grant (StG), PE2, ERC-2011-StG_20101014
Summary Understanding the many-body physics of strongly correlated systems has always been a major challenge for theoretical and experimental physics. The recent advances in the field of ultracold quantum gases have opened a completely new way to study such strongly correlated systems. It is now feasible to use ultracold gases as quantum simulators for such diverse systems such as the Hubbard model or the BCS-BEC crossover. The objective of this project is to study a three-component Fermi gas in an optical lattice, a system with rich many-body physics. With our experiments we aim to contribute to the understanding of exotic phases which are discussed in the context of QCD and condensed matter physics.
Summary
Understanding the many-body physics of strongly correlated systems has always been a major challenge for theoretical and experimental physics. The recent advances in the field of ultracold quantum gases have opened a completely new way to study such strongly correlated systems. It is now feasible to use ultracold gases as quantum simulators for such diverse systems such as the Hubbard model or the BCS-BEC crossover. The objective of this project is to study a three-component Fermi gas in an optical lattice, a system with rich many-body physics. With our experiments we aim to contribute to the understanding of exotic phases which are discussed in the context of QCD and condensed matter physics.
Max ERC Funding
1 469 040 €
Duration
Start date: 2011-08-01, End date: 2016-07-31
Project acronym ACOPS
Project Advanced Coherent Ultrafast Laser Pulse Stacking
Researcher (PI) Jens Limpert
Host Institution (HI) FRIEDRICH-SCHILLER-UNIVERSITAT JENA
Call Details Consolidator Grant (CoG), PE2, ERC-2013-CoG
Summary "An important driver of scientific progress has always been the envisioning of applications far beyond existing technological capabilities. Such thinking creates new challenges for physicists, driven by the groundbreaking nature of the anticipated application. In the case of laser physics, one of these applications is laser wake-field particle acceleration and possible future uses thereof, such as in collider experiments, or for medical applications such as cancer treatment. To accelerate electrons and positrons to TeV-energies, a laser architecture is required that allows for the combination of high efficiency, Petawatt peak powers, and Megawatt average powers. Developing such a laser system would be a challenging task that might take decades of aggressive research, development, and, most important, revolutionary approaches and innovative ideas.
The goal of the ACOPS project is to develop a compact, efficient, scalable, and cost-effective high-average and high-peak power ultra-short pulse laser concept.
The proposed approach to this goal relies on the spatially and temporally separated amplification of ultrashort laser pulses in waveguide structures, followed by coherent combination into a single train of pulses with increased average power and pulse energy. This combination can be realized through the coherent addition of the output beams of spatially separated amplifiers, combined with the pulse stacking of temporally separated pulses in passive enhancement cavities, employing a fast-switching element as cavity dumper.
Therefore, the three main tasks are the development of kW-class high-repetition-rate driving lasers, the investigation of non-steady state pulse enhancement in passive cavities, and the development of a suitable dumping element.
If successful, the proposed concept would undoubtedly provide a tool that would allow researchers to surpass the current limits in high-field physics and accelerator science."
Summary
"An important driver of scientific progress has always been the envisioning of applications far beyond existing technological capabilities. Such thinking creates new challenges for physicists, driven by the groundbreaking nature of the anticipated application. In the case of laser physics, one of these applications is laser wake-field particle acceleration and possible future uses thereof, such as in collider experiments, or for medical applications such as cancer treatment. To accelerate electrons and positrons to TeV-energies, a laser architecture is required that allows for the combination of high efficiency, Petawatt peak powers, and Megawatt average powers. Developing such a laser system would be a challenging task that might take decades of aggressive research, development, and, most important, revolutionary approaches and innovative ideas.
The goal of the ACOPS project is to develop a compact, efficient, scalable, and cost-effective high-average and high-peak power ultra-short pulse laser concept.
The proposed approach to this goal relies on the spatially and temporally separated amplification of ultrashort laser pulses in waveguide structures, followed by coherent combination into a single train of pulses with increased average power and pulse energy. This combination can be realized through the coherent addition of the output beams of spatially separated amplifiers, combined with the pulse stacking of temporally separated pulses in passive enhancement cavities, employing a fast-switching element as cavity dumper.
Therefore, the three main tasks are the development of kW-class high-repetition-rate driving lasers, the investigation of non-steady state pulse enhancement in passive cavities, and the development of a suitable dumping element.
If successful, the proposed concept would undoubtedly provide a tool that would allow researchers to surpass the current limits in high-field physics and accelerator science."
Max ERC Funding
1 881 040 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym AMPLITUDES
Project Novel structures in scattering amplitudes
Researcher (PI) Johannes Martin HENN
Host Institution (HI) JOHANNES GUTENBERG-UNIVERSITAT MAINZ
Call Details Consolidator Grant (CoG), PE2, ERC-2016-COG
Summary This project focuses on developing quantum field theory methods and applying them to the phenomenology of elementary particles. At the Large Hadron Collider (LHC) our current best theoretical understanding of particle physics is being tested against experiment by measuring e.g. properties of the recently discovered Higgs boson. With run two of the LHC, currently underway, the experimental accuracy will further increase. Theoretical predictions matching the latter are urgently needed. Obtaining these requires extremely difficult calculations of scattering amplitudes and cross sections in quantum field theory, including calculations to correctly describe large contributions due to long-distance physics in the latter. Major obstacles in such computations are the large number of Feynman diagrams that are difficult to handle, even with the help of modern computers, and the computation of Feynman loop integrals. To address these issues, we will develop innovative methods that are inspired by new structures found in supersymmetric field theories. We will extend the scope of the differential equations method for computing Feynman integrals, and apply it to scattering processes that are needed for phenomenology, but too complicated to analyze using current methods. Our results will help measure fundamental parameters of Nature, such as, for example, couplings of the Higgs boson, with unprecedented precision. Moreover, by accurately predicting backgrounds from known physics, our results will also be invaluable for searches of new particles.
Summary
This project focuses on developing quantum field theory methods and applying them to the phenomenology of elementary particles. At the Large Hadron Collider (LHC) our current best theoretical understanding of particle physics is being tested against experiment by measuring e.g. properties of the recently discovered Higgs boson. With run two of the LHC, currently underway, the experimental accuracy will further increase. Theoretical predictions matching the latter are urgently needed. Obtaining these requires extremely difficult calculations of scattering amplitudes and cross sections in quantum field theory, including calculations to correctly describe large contributions due to long-distance physics in the latter. Major obstacles in such computations are the large number of Feynman diagrams that are difficult to handle, even with the help of modern computers, and the computation of Feynman loop integrals. To address these issues, we will develop innovative methods that are inspired by new structures found in supersymmetric field theories. We will extend the scope of the differential equations method for computing Feynman integrals, and apply it to scattering processes that are needed for phenomenology, but too complicated to analyze using current methods. Our results will help measure fundamental parameters of Nature, such as, for example, couplings of the Higgs boson, with unprecedented precision. Moreover, by accurately predicting backgrounds from known physics, our results will also be invaluable for searches of new particles.
Max ERC Funding
2 000 000 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym assemblyNMR
Project 3D structures of bacterial supramolecular assemblies by solid-state NMR
Researcher (PI) Adam Lange
Host Institution (HI) FORSCHUNGSVERBUND BERLIN EV
Call Details Starting Grant (StG), LS1, ERC-2013-StG
Summary Supramolecular assemblies – formed by the self-assembly of hundreds of protein subunits – are part of bacterial nanomachines involved in key cellular processes. Important examples in pathogenic bacteria are pili and type 3 secretion systems (T3SS) that mediate adhesion to host cells and injection of virulence proteins. Structure determination at atomic resolution of such assemblies by standard techniques such as X-ray crystallography or solution NMR is severely limited: Intact T3SSs or pili cannot be crystallized and are also inherently insoluble. Cryo-electron microscopy techniques have recently made it possible to obtain low- and medium-resolution models, but atomic details have not been accessible at the resolution obtained in these studies, leading sometimes to inaccurate models.
I propose to use solid-state NMR (ssNMR) to fill this knowledge-gap. I could recently show that ssNMR on in vitro preparations of Salmonella T3SS needles constitutes a powerful approach to study the structure of this virulence factor. Our integrated approach also included results from electron microscopy and modeling as well as in vivo assays (Loquet et al., Nature 2012). This is the foundation of this application. I propose to extend ssNMR methodology to tackle the structures of even larger or more complex homo-oligomeric assemblies with up to 200 residues per monomeric subunit. We will apply such techniques to address the currently unknown 3D structures of type I pili and cytoskeletal bactofilin filaments. Furthermore, I want to develop strategies to directly study assemblies in a native-like setting. As a first application, I will study the 3D structure of T3SS needles when they are complemented with intact T3SSs purified from Salmonella or Shigella. The ultimate goal of this proposal is to establish ssNMR as a generally applicable method that allows solving the currently unknown structures of bacterial supramolecular assemblies at atomic resolution.
Summary
Supramolecular assemblies – formed by the self-assembly of hundreds of protein subunits – are part of bacterial nanomachines involved in key cellular processes. Important examples in pathogenic bacteria are pili and type 3 secretion systems (T3SS) that mediate adhesion to host cells and injection of virulence proteins. Structure determination at atomic resolution of such assemblies by standard techniques such as X-ray crystallography or solution NMR is severely limited: Intact T3SSs or pili cannot be crystallized and are also inherently insoluble. Cryo-electron microscopy techniques have recently made it possible to obtain low- and medium-resolution models, but atomic details have not been accessible at the resolution obtained in these studies, leading sometimes to inaccurate models.
I propose to use solid-state NMR (ssNMR) to fill this knowledge-gap. I could recently show that ssNMR on in vitro preparations of Salmonella T3SS needles constitutes a powerful approach to study the structure of this virulence factor. Our integrated approach also included results from electron microscopy and modeling as well as in vivo assays (Loquet et al., Nature 2012). This is the foundation of this application. I propose to extend ssNMR methodology to tackle the structures of even larger or more complex homo-oligomeric assemblies with up to 200 residues per monomeric subunit. We will apply such techniques to address the currently unknown 3D structures of type I pili and cytoskeletal bactofilin filaments. Furthermore, I want to develop strategies to directly study assemblies in a native-like setting. As a first application, I will study the 3D structure of T3SS needles when they are complemented with intact T3SSs purified from Salmonella or Shigella. The ultimate goal of this proposal is to establish ssNMR as a generally applicable method that allows solving the currently unknown structures of bacterial supramolecular assemblies at atomic resolution.
Max ERC Funding
1 456 000 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym BACTERIAL SYRINGES
Project Protein Translocation Through Bacterial Syringes
Researcher (PI) Stefan Raunser
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Consolidator Grant (CoG), LS1, ERC-2013-CoG
Summary "The main objective of this application is to study the molecular basis of cellular infection by bacterial ABC-type toxins (Tc). Tc complexes are important virulence factors of a range of bacteria, including Photorhabdus luminescens and Yersinia pseudotuberculosis that infect insects and humans. Belonging to the class of pore-forming toxins, tripartite Tc complexes perforate the host membrane by forming channels that translocate toxic enzymes into the host.
In our previous cryo-EM work on the P. luminescens Tc complex we discovered that Tcs use a special syringe-like device for cell entry. Building on these results, we now intend to unravel the molecular mechanism through which this unusual and complicated injection system allows membrane permeation and protein translocation. We will use a hybrid approach, including biochemical reconstitution, structural analysis by cryo-EM and X-ray crystallography, fluorescence-based assays and site-directed mutagenesis to provide a comprehensive description of the molecular mechanism of infection at an unprecedented level of molecular detail.
Our results will be paradigmatic for understanding the mechanism of action of ABC-type toxins and will shed new light on the interactions of bacterial pathogens with their hosts."
Summary
"The main objective of this application is to study the molecular basis of cellular infection by bacterial ABC-type toxins (Tc). Tc complexes are important virulence factors of a range of bacteria, including Photorhabdus luminescens and Yersinia pseudotuberculosis that infect insects and humans. Belonging to the class of pore-forming toxins, tripartite Tc complexes perforate the host membrane by forming channels that translocate toxic enzymes into the host.
In our previous cryo-EM work on the P. luminescens Tc complex we discovered that Tcs use a special syringe-like device for cell entry. Building on these results, we now intend to unravel the molecular mechanism through which this unusual and complicated injection system allows membrane permeation and protein translocation. We will use a hybrid approach, including biochemical reconstitution, structural analysis by cryo-EM and X-ray crystallography, fluorescence-based assays and site-directed mutagenesis to provide a comprehensive description of the molecular mechanism of infection at an unprecedented level of molecular detail.
Our results will be paradigmatic for understanding the mechanism of action of ABC-type toxins and will shed new light on the interactions of bacterial pathogens with their hosts."
Max ERC Funding
1 999 992 €
Duration
Start date: 2014-07-01, End date: 2019-06-30
Project acronym BinGraSp
Project Modeling the Gravitational Spectrum of Neutron Star Binaries
Researcher (PI) Sebastiano Bernuzzi
Host Institution (HI) FRIEDRICH-SCHILLER-UNIVERSITAT JENA
Call Details Starting Grant (StG), PE2, ERC-2016-STG
Summary The most energetic electromagnetic phenomena in the Universe are believed to be powered by the collision of two neutron stars, the smallest and densest stars on which surface gravity is about 2 billion times stronger than gravity on Earth. However, a definitive identification of neutron star mergers as central engines for short-gamma-ray bursts and kilonovae transients is possible only by direct gravitational-wave observations. The latter provide us with unique information on neutron stars' masses, radii, and spins, including the possibility to set the strongest observational constraints on the unknown equation-of-state of matter at supranuclear densities.
Neutron stars binary mergers are among the main targets for ground-based gravitational-wave interferometers like Advanced LIGO and Virgo, which start operations this year. The astrophysical data analysis of the signals emitted by these sources requires the availability of accurate waveform models, which are missing to date. Hence, the theoretical understanding of the gravitational spectrum is a necessary and urgent step for the development of a gravitational-based astrophysics in the next years.
This project aims at developing, for the first time, a precise theoretical model for the complete gravitational spectrum of neutron star binaries, including the merger and postmerger stages of the coalescence process. Building on the PI's unique expertise and track record, the proposed research exploits synergy between analytical and numerical methods in General Relativity. Results from state of the art nonlinear 3D numerical relativity simulations will be combined with the most advanced analytical framework for the relativistic two-body problem. The model developed here will be used in the first gravitational-wave observations and will dramatically impact multimessenger astrophysics.
Summary
The most energetic electromagnetic phenomena in the Universe are believed to be powered by the collision of two neutron stars, the smallest and densest stars on which surface gravity is about 2 billion times stronger than gravity on Earth. However, a definitive identification of neutron star mergers as central engines for short-gamma-ray bursts and kilonovae transients is possible only by direct gravitational-wave observations. The latter provide us with unique information on neutron stars' masses, radii, and spins, including the possibility to set the strongest observational constraints on the unknown equation-of-state of matter at supranuclear densities.
Neutron stars binary mergers are among the main targets for ground-based gravitational-wave interferometers like Advanced LIGO and Virgo, which start operations this year. The astrophysical data analysis of the signals emitted by these sources requires the availability of accurate waveform models, which are missing to date. Hence, the theoretical understanding of the gravitational spectrum is a necessary and urgent step for the development of a gravitational-based astrophysics in the next years.
This project aims at developing, for the first time, a precise theoretical model for the complete gravitational spectrum of neutron star binaries, including the merger and postmerger stages of the coalescence process. Building on the PI's unique expertise and track record, the proposed research exploits synergy between analytical and numerical methods in General Relativity. Results from state of the art nonlinear 3D numerical relativity simulations will be combined with the most advanced analytical framework for the relativistic two-body problem. The model developed here will be used in the first gravitational-wave observations and will dramatically impact multimessenger astrophysics.
Max ERC Funding
1 432 301 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym CelluFuel
Project Designer Cellulosomes by Single Molecule Cut & Paste
Researcher (PI) Hermann Eduard Gaub
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), LS1, ERC-2011-ADG_20110310
Summary Biofuel from wood and waste will be a substantial share of our future energy mix. The conversion of lignocellulose to fermentable polysaccharides is the current bottleneck. We propose to use single molecule cut and paste technology to assemble designer cellulosoms and combine enzymes from different species with nanocatalysts.
Summary
Biofuel from wood and waste will be a substantial share of our future energy mix. The conversion of lignocellulose to fermentable polysaccharides is the current bottleneck. We propose to use single molecule cut and paste technology to assemble designer cellulosoms and combine enzymes from different species with nanocatalysts.
Max ERC Funding
2 351 450 €
Duration
Start date: 2012-03-01, End date: 2018-02-28
Project acronym COMPLEXNMD
Project NMD Complexes: Eukaryotic mRNA Quality Control
Researcher (PI) Christiane Helene Berger-Schaffitzel
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Call Details Starting Grant (StG), LS1, ERC-2011-StG_20101109
Summary Nonsense-mediated mRNA decay (NMD) is an essential mechanism controlling translation in the eukaryotic cell. NMD ascertains accurate expression of the genetic information by quality controlling messenger RNA (mRNA). During translation, NMD factors recognize and target to degradation aberrant mRNAs that have a premature stop codon (PTC) and that would otherwise lead to the production of truncated proteins which could be harmful for the cell. A wide range of genetic diseases have their origin in the mechanisms of NMD. Discrimination of a PTC from a correct termination codon depends on splicing and translation, and it is the first and foremost step in human NMD. The molecular mechanism of this process remains elusive to date.
In the research proposed, I will undertake to elucidate the molecular basis of translation termination and induction of NMD. I will study complexes involved in human translation termination at a normal stop codon and involved in NMD. I will employ an array of innovative techniques including recombinant production of human protein complexes by the MultiBac system, mammalian in vitro translation, mass spectrometry for detecting relevant protein modifications, biophysical techniques, mutational analyses and RNA-interference experiments. Stable ribosomal complexes with termination factors and complexes of NMD factors will be used for structure determination by cryo-electron microscopy. State-of-the-art image processing will be applied to address the inherent heterogeneity of the complexes. Hybrid approaches will allow the combination of cryo-EM structures with existing high-resolution structures of factors involved for generation of quasi-atomic models thereby visualizing molecular mechanisms of NMD action. This interdisciplinary work will foster our understanding at a molecular level of a paramount step in mRNA quality control, which is a vital prerequisite for the development of new treatment strategies in NMD-related diseases.
Summary
Nonsense-mediated mRNA decay (NMD) is an essential mechanism controlling translation in the eukaryotic cell. NMD ascertains accurate expression of the genetic information by quality controlling messenger RNA (mRNA). During translation, NMD factors recognize and target to degradation aberrant mRNAs that have a premature stop codon (PTC) and that would otherwise lead to the production of truncated proteins which could be harmful for the cell. A wide range of genetic diseases have their origin in the mechanisms of NMD. Discrimination of a PTC from a correct termination codon depends on splicing and translation, and it is the first and foremost step in human NMD. The molecular mechanism of this process remains elusive to date.
In the research proposed, I will undertake to elucidate the molecular basis of translation termination and induction of NMD. I will study complexes involved in human translation termination at a normal stop codon and involved in NMD. I will employ an array of innovative techniques including recombinant production of human protein complexes by the MultiBac system, mammalian in vitro translation, mass spectrometry for detecting relevant protein modifications, biophysical techniques, mutational analyses and RNA-interference experiments. Stable ribosomal complexes with termination factors and complexes of NMD factors will be used for structure determination by cryo-electron microscopy. State-of-the-art image processing will be applied to address the inherent heterogeneity of the complexes. Hybrid approaches will allow the combination of cryo-EM structures with existing high-resolution structures of factors involved for generation of quasi-atomic models thereby visualizing molecular mechanisms of NMD action. This interdisciplinary work will foster our understanding at a molecular level of a paramount step in mRNA quality control, which is a vital prerequisite for the development of new treatment strategies in NMD-related diseases.
Max ERC Funding
1 176 825 €
Duration
Start date: 2012-02-01, End date: 2016-11-30
Project acronym CREMA
Project Charge radius experiment with muonic atoms
Researcher (PI) Randolf Pohl
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Starting Grant (StG), PE2, ERC-2011-StG_20101014
Summary "A measurement of the 2S-2P transition frequencies (Lamb shift) in the muonic helium-3 and 4 ions by means of laser spectroscopy is proposed. This will lead to a ten times more accurate determination of the root-mean-square (rms) charge radii of the He-3 and He-4 nuclei. The radius of the magnetic moment distribution inside the He-3 nucleus will result from the hyperfine structure in muonic 3He.
In the muonic helium ion, a single negative muon orbits the helium nucleus. The muon is a point-like lepton, just as the electron, except it is about 200 times heavier. This gives a factor of 200^3 = 10^7 enhancement of nuclear finite size effects on the energy levels of muonic vs. regular (electonic) Helium ions. Muonic helium is the ideal sytem to study the He nuclear size.
The CREMA project has four main aims:
(1) Solve the ""proton size puzzle"" created by our recently completed muonic hydrogen project [R. Pohl et al., ""The size of the proton"", Nature 466, 213 (2010)]. Our tenfold improvement of the proton charge radius resulted in a five sigma discrepancy with the 2006 CODATA value, which is mostly based on hydrogen spectroscopy. This poses a serious challenge to bound-state QED, and may even point towards new physics. CREMA will help to clarify this.
(2) Absolute nuclear charge radii of all helium isotopes He-3,4,6,8 will result from CREMA. The charge radius differences are precisely known, but the absolute size of the He-4 anchor nucleus can best be measured in muonic helium. Absolute charge radii are a more stringent benchmark for few-nucleon nuclear models than the radius difference.
(3) Test of bound-state QED: Spectroscopy of regular He+ ions is underway. He+ (Z=2) is more sensitive than hydrogen (Z=1) to higher-order QED contributions which scale as Z^5. An accurate He charge radius from CREMA is mandatory for this.
(4) An improved value of the Rydberg constant will result from the He+ spectroscopy only with the improved charge radius from CREMA."
Summary
"A measurement of the 2S-2P transition frequencies (Lamb shift) in the muonic helium-3 and 4 ions by means of laser spectroscopy is proposed. This will lead to a ten times more accurate determination of the root-mean-square (rms) charge radii of the He-3 and He-4 nuclei. The radius of the magnetic moment distribution inside the He-3 nucleus will result from the hyperfine structure in muonic 3He.
In the muonic helium ion, a single negative muon orbits the helium nucleus. The muon is a point-like lepton, just as the electron, except it is about 200 times heavier. This gives a factor of 200^3 = 10^7 enhancement of nuclear finite size effects on the energy levels of muonic vs. regular (electonic) Helium ions. Muonic helium is the ideal sytem to study the He nuclear size.
The CREMA project has four main aims:
(1) Solve the ""proton size puzzle"" created by our recently completed muonic hydrogen project [R. Pohl et al., ""The size of the proton"", Nature 466, 213 (2010)]. Our tenfold improvement of the proton charge radius resulted in a five sigma discrepancy with the 2006 CODATA value, which is mostly based on hydrogen spectroscopy. This poses a serious challenge to bound-state QED, and may even point towards new physics. CREMA will help to clarify this.
(2) Absolute nuclear charge radii of all helium isotopes He-3,4,6,8 will result from CREMA. The charge radius differences are precisely known, but the absolute size of the He-4 anchor nucleus can best be measured in muonic helium. Absolute charge radii are a more stringent benchmark for few-nucleon nuclear models than the radius difference.
(3) Test of bound-state QED: Spectroscopy of regular He+ ions is underway. He+ (Z=2) is more sensitive than hydrogen (Z=1) to higher-order QED contributions which scale as Z^5. An accurate He charge radius from CREMA is mandatory for this.
(4) An improved value of the Rydberg constant will result from the He+ spectroscopy only with the improved charge radius from CREMA."
Max ERC Funding
1 499 976 €
Duration
Start date: 2011-11-01, End date: 2016-10-31
Project acronym CRYOTRANSLATION
Project High Resolution cryo-EM Analysis of Ribosome-associated Functions
Researcher (PI) Roland Beckmann
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), LS1, ERC-2011-ADG_20110310
Summary "Translation of the genetically encoded information into polypeptides, protein biosynthesis, is a central function executed by ribosomes in all cells. In the case of membrane protein synthesis, integration into the membrane usually occurs co-translationally and requires a ribosome-associated translocon (SecYEG/Sec61). This highly coordinated process is poorly understood, since high-resolution structural information is lacking. Although single particle cryo-electron microscopy (cryo-EM) has given invaluable structural insights for such dynamic ribosomal complexes, the resolution is so far limited to 5-10 Å for asymmetrical particles. Thus, the mechanistic depth and reliability of interpretation has accordingly been limited.
Here, I propose to use single particle cryo-EM at improved, molecular resolution of 3-4 Å to study two fundamental ribosome-associated processes:
(i) co-translational integration of polytopic membrane proteins and
(ii) recycling of the eukaryotic ribosome.
First, we will visualize nascent polytopic membrane proteins inserting into the lipid bilayer via the bacterial ribosome-bound SecYEG translocon. Notably, the translocon will be embedded in a lipid environment provided by so-called nanodiscs. Second, we will visualize in a similar approach membrane protein insertion via the YidC insertase, the main alternative translocon. Third, as a novel research direction, we will determine the structure and function of eukaryotic ribosome recycling complexes involving the ABC-ATPase RLI.
The results will allow, together with functional biochemical data, an in-depth molecular structure-function analysis of these fundamental ribosome-associated processes. Moreover, reaching molecular resolution for asymmetrical particles by single particle cryo-EM will lift this technology to a level of analytical power approaching X-ray and NMR methods. ERC funding would allow for this highly challenging research to be conducted in an internationally competitive way in Europe."
Summary
"Translation of the genetically encoded information into polypeptides, protein biosynthesis, is a central function executed by ribosomes in all cells. In the case of membrane protein synthesis, integration into the membrane usually occurs co-translationally and requires a ribosome-associated translocon (SecYEG/Sec61). This highly coordinated process is poorly understood, since high-resolution structural information is lacking. Although single particle cryo-electron microscopy (cryo-EM) has given invaluable structural insights for such dynamic ribosomal complexes, the resolution is so far limited to 5-10 Å for asymmetrical particles. Thus, the mechanistic depth and reliability of interpretation has accordingly been limited.
Here, I propose to use single particle cryo-EM at improved, molecular resolution of 3-4 Å to study two fundamental ribosome-associated processes:
(i) co-translational integration of polytopic membrane proteins and
(ii) recycling of the eukaryotic ribosome.
First, we will visualize nascent polytopic membrane proteins inserting into the lipid bilayer via the bacterial ribosome-bound SecYEG translocon. Notably, the translocon will be embedded in a lipid environment provided by so-called nanodiscs. Second, we will visualize in a similar approach membrane protein insertion via the YidC insertase, the main alternative translocon. Third, as a novel research direction, we will determine the structure and function of eukaryotic ribosome recycling complexes involving the ABC-ATPase RLI.
The results will allow, together with functional biochemical data, an in-depth molecular structure-function analysis of these fundamental ribosome-associated processes. Moreover, reaching molecular resolution for asymmetrical particles by single particle cryo-EM will lift this technology to a level of analytical power approaching X-ray and NMR methods. ERC funding would allow for this highly challenging research to be conducted in an internationally competitive way in Europe."
Max ERC Funding
2 995 640 €
Duration
Start date: 2012-05-01, End date: 2017-04-30
