Yearbooks of the Max Planck Society

Yearbooks of the Max Planck Society

2018

  • Molecular Resolution in Optical Microscopy

    2018 Hell, Stefan W.
    For the first time, it has been demonstrated that the ultimate resolution limit in fluorescence microscopy – the molecule’s size itself – can also practically be achieved. The MINFLUX concept begins a new chapter and opens up unprecedented opportunities in the optical analysis of molecular systems.

2017

  • The sleeping worm

    2017 Bringmann, Henrik
    The question how and why we sleep is one of the most exciting mysteries of biology. Sleep is important for our well-being. Yet, we do not know how sleep becomes regenerative. The Max Planck Research Group Sleep and Waking is trying to answer these basic questions. The researchers’ strategy is to first investigate sleep in one of the most simple model organisms that sleeps, the roundworm Caenorhabditis elegans. The group identified a single neuron to be responsible for sleep induction and found a molecular mechanism for sleep induction.
  • Towards disease modifying therapies of neurodegenerative diseases

    2017 Ryazanov, Sergey;  Leonov, Andrei; Griesinger, Christian
    Neurodegenerative diseases‘ hallmark is the aggregation of mostly intrinsically disordered proteins. Getting fundamental insights into the structural biology of these proteins, it was possible to identify oligomers as an attractive target for disease modifying therapies. The compound anle138b is bearing the required properties regarding modification of aggregation pathways, and is also orally bioavailable.

2016

  • Protons as sensitive reporters for molecular details

    2016 Linser, Rasmus
    Many proteins in the focus of structural-biology studies cannot be elucidated by conventional methodology. The research group Solid-State NMR hence is concerned with the development and application of NMR (nuclear magnetic resonance) methods dedicated for the characterization of structure and dynamics of solid proteins. Developing improved methodology for solid-state NMR helps to make more targets amenable for their characterization with atomic resolution.
  • How genes get active

    2016 Cramer, Patrick
    Genes must be activated to make use of the genetic information in living cells. Gene activation starts with a process called transcription, which produces RNA copies of genes. Transcription by the transcribing enzymes, the RNA polymerases, has now been resolved in atomic detail. Future research will concentrate on processes that regulate transcription and thereby govern gene activity during cellular differentiation and the development of tissues and organisms.

2015

  • Bunch-compression of ultra-short hydrogen atom pulses

    2015 Schwarzer, Dirk; Wodtke, Alec
    Ultra-short laser pulses enable studies of light-induced chemical processes with extremely high time resolution. However, most chemical events are not initiated by light, but rather by collisions. Time-resolved collisional experiments require ultra-short pulses of atoms and molecules. Very intense ultra-short hydrogen atom pulses as short as 1.2 nanoseconds were generated by bunch-compression for the first time.
  • Not just “On and Off”: micro-RNAs fine tune gene expression

    2015 Shcherbata, Halyna R.
    The research group Gene Expression and Signaling investigates the various functions of micro-RNAs (miRNAs) under stress or pathological conditions using the fruit fly Drosophila melanogaster as a model for human diseases. miRNA-based regulatory networks buffer mistakes or stochastic fluctuations during gene expression to maintain cell identity and control differentiation, ensuring that each cell is equipped with the correct repertoire of proteins and fulfills its particular tasks.

2014

  • Structure elucidation of supramolecular protein assemblies by solid-state NMR

    2014 Lange, Adam
    In the last decade, magnetic resonance in the solid state (solid-state NMR) has emerged as a powerful technique in structural biology as it gives access to structural information for systems which are insoluble or do not crystallize easily. For example, functional filamentous assemblies such as the needle of the type three secretion system (T3SS) – composed of multiple copies of a single small protein – can be readily studied.
  • The ribosome: a versatile mega-ribozyme

    2014 Rodnina, Marina V.
    The catalytic center of ribosomes is made up of ribonucleic acid (RNA). Catalysis is predominantly by orienting the substrates. The catalytic center is quite flexible; besides assembling amino acids to form proteins it catalyzes the hydrolytic liberation of the proteins after completion and accepts unnatural amino acids. This is utilized in Biotechnology for synthesizing proteins with particular properties. Peptide bond formation usually takes place spontaneously. However, linking several proline residues requires a special translation factor.

2013

  • Macromolecular machines in 3D: The complex world of complexes

    2013 Stark, Holger

    Tiny nano machines called macromolecular complexes participate in the most fundamental biological processes. The high-resolution three-dimensional (3D) structure of these complexes and their dynamic behavior can be studied by cryo electron microscopy. The molecular movies that can be obtained for these nano machines contribute tremendously to our understanding of molecular processes at a structural level.

  • How neurons talk to each other – molecular machines at work

    2013 Jahn, Reinhard
    Neurons are connected with each other by synapses where signaling is mediated by neurotransmitters. In the sender neuron, these transmitters are stored in synaptic vesicles and released by calcium-dependent exocytosis. A quantitative molecular model of a prototype synaptic vesicle has been established. Moreover, the structure of the SNARE-proteins responsible for exocytosis was solved. Reconstitution of the proteins in artificial membranes allowed for a refined understanding of their regulation by calcium and for an identification of intermediate steps in exocytotic membrane fusion.

2012

  • Nano particles on the scales

    2012 Burg, Thomas
    A wide variety of problems in science and technology is concerned with the study of biological and synthetic nanoparticles. Being less than one hundred nanometers in size, such objects often elude conventional techniques of detection and measurement. Nanofluidic resonators have recently enabled the direct weighing of single nanoparticles and the measurement of size distributions in complex liquid samples. Such measurements are important to help advance our understanding of many fundamental processes in biophysics, medicine, biology, biotechnolgy.
  • Structure and function of spliceosomes

    2012 Lührmann, Reinhard
    Eukaryotic pre-mRNAs contain non-coding regions (introns) which need to be removed before the mRNA can be used for the synthesis of proteins. This so-called splicing process is catalysed in the cell's nucleus by the spliceosome, a highly complex and dynamic molecular machine. It is composed of numerous protein and RNA components and it is assembled anew on each intron to be removed from an RNA transcript. Using approaches from biochemistry, molecular biology, genetics and structural biology, we study the complex catalytic work cycle of the spliceosome to understand its structure and function.

2011

  • DNA enzymes as tools for the synthesis of chemically modified RNA

    2011 Höbartner, Claudia
    The synthesis of chemically modified RNA is often a prerequisite for biophysical investigations of RNA and RNA-protein interactions. Solid-phase synthesis enables site-specific modification of relatively short RNA oligonucleotides. Larger modified RNA targets are accessible by a combination of chemical and enzymatic approaches. DNA enzymes are artificial catalytically active DNA molecules that have been identified by in vitro selection from random DNA pools. DNA enyzmes can be used for the ligation of RNA fragments and are currently developed into tools for the direct modification of RNA.
  • Chemical elementary processes between micro- and macrocosm

    2011 Troe, Jürgen
    Chemical transformations of matter often are composed in a complicated way by elementary chemical processes. Such processes may be separated in the laboratory and characterized with respect to their time dependence, their kinetics and dynamics. The results enter large data bases which are used for modelling of complex natural phenomena as well as for optimization of technical systems. Reactions of hydrogen atoms with molecular oxygen, fragmentations of molecular ions and reactions of electrons with sulphur hexafluoride are chosen as illustrative examples.

2010

  • Lock pick or bunch of keys: what proteins and safecrackers have in common

    2010 Griesinger, Christian
    Novel NMR spectroscopic parameters allowed to determine not only the average structure of the protein ubiquitin but in addition the description of a faithful ensemble of the protein in solution. The ensemble reflected especially the previously inaccessible time window between 5 ns and 50 µs. The ensemble revealed the mechanism of protein protein recognition for this protein. If this was general new strategies for modulation of protein protein recognition would open up that could be used for more efficient drug development.
  • Electron spins as probes for biomolecules

    2010 Tkach, Igor und Bennati, Marina
    Unpaired electrons possess a magnetic moment, which is about three orders of magnitude larger than the one of a proton. This moment can be employed as a highly sensitive probe in EPR spectroscopic investigations to gain structural information at the atomic up to the nanometer scale. The experiments provide insights into structural changes of biomolecules during their functional states. We have developed and implemented multi-frequency EPR methodologies to investigate enzymatic reactions in proteins and oligonucleotides.

2009

  • Epigenetics: Regulation of gene activity by histone modifications

    2009 Fischle, Wolfgang
    In all cells of our bodies DNA is found complexed with basic proteins, the so-called histones. These proteins not only organize and protect the genetic information, but are also crucially involved in all biological processes involving DNA. In this aspect, a large number of different post-translational histone modifications direct the availability and accessibility of the DNA. While many histone modifications could be linked to different biological phenomena and signal transduction pathways, the molecular working mechanisms of most histone modifications are still not understood.
  • Logistics on smallest possible space: Transport processes between cell nucleus and cytoplasm

    2009 Dirk Görlich; Steffen Frey
    The cell nucleus is enclosed by the nuclear envelope, lacks protein synthesis and therefore imports each and every protein from the cytosol. Conversely, the nucleus supplies the cytoplasm with nuclear products, such as ribosomes, tRNAs and mRNAs. The permeability barrier of nuclear pore complexes controls all this exchange. This permeability barrier is an "intelligent" hydrogel with truly remarkable properties. It excludes inert macromolecules, but permits an up to 20 000-fold faster entry of cargoes, when these are bound to appropriate nuclear transport receptors.

2008

  • The genetic network of the circadian clock coordinates the communication between the organism and its environment

    2008 Eichele, Gregor; Oster, Henrik
    Circadian clocks regulate a plethora of physiological processes including the sleep/wake cycle, blood pressure and body temperature. Such clocks enable organisms to adjust to the 24-hour day/night cycle resulting from the rotation of the earth. Virtually all living beings have a circadian clock and in the case of multicellular organisms, most cell types house such a clock. The clock mechanism consists of a stable network of genes and proteins that mutually regulate each other, thereby not only establishing a self-sustaining clockwork but enabling this clock to adjust to periodic environmental changes such as availability of light and access to food.
  • Molecular complexes investigated by high-resolution solid-state Magnetic Resonance spectroscopy

    2008 Baldus, Marc
    Many chemical or biophysical processes involve molecules that are insoluble or non-crystalline. Consider, for instance, the functional control of membrane proteins by external ligands or the formation of protein aggregates in the context of Alzheimer´s or Parkinson’s disease. In such systems, solid-state NMR can offer unique possibilities to elucidate structural or dynamic parameters at atomic resolution.

2007

  • Release of neurotransmitters and hormones: similar and totally different

    2007 Neher, Erwin
    The release of signalling molecules from a variety of cell types proceeds along very similar lines. In nerve endings neurotransmitter is stored in membrane bound containers, so called vesicles. It is released on arrival of a nerve impulse by the process of exocytosis, i. e. fusion of the vesicle with the cellular membrane. Release of hormones from gland cells follows a similar pattern. The underlying cellular mechanisms utilize the same molecular building blocks in both systems. Nevertheless, the regulation of both processes turns out to be very different on close inspection. Most of these differences may reside in the fact, that at nerve endings the most important players – vesicles and calcium specific ion channels – are linked together in a highly-regulated and specific fashion.
  • Magnetic Resonance Imaging in Neurobiology – From Mouse to Human

    2007 Frahm, Jens
    Research of the Biomedical NMR unit focuses on the further development of magnetic resonance imaging and advanced applications in neurobiology. Pertinent approaches allow for unique insights into the structure, metabolism, and function of the intact living brain – from mouse to human. Specific projects range from novel image encoding and reconstruction techniques to animal models of neurodegenerative disease and functional assessments of neuroaxonal connectivity and cognitive information processing in humans.

2006

  • The JAK/STAT signalling pathway

    2006 Zeidler, Martin
    The development of a complex animal from a single egg cell requires both cell division and cell specialization to produce the different organs and structures required for adult life. In order to be able to complete such developmental programs cells must be able to receive and correctly interpret instructions; instructions that are mediated by a relatively small group of evolutionarily conserved signal transduction pathways. One of these, and the focus of research in the laboratory of Martin Zeidler, MPI for Biophysical Chemistry in Göttingen, is the JAK/STAT pathway. The JAK/STAT signalling pathway plays important roles during early embryonic development and is required for the production of blood cells and the function of the immune system. Furthermore, its mis-activation is responsible for a large proportion of human leukaemias and lymphomas. As such, a better understanding of the pathway and the mechanisms that control its activity is potentially significant to human health. Zeidler and his colleagues use the evolutionary conservation common to all signalling pathways to identify and characterise the regulators of JAK/STAT signalling in the fruit fly Drosophila melanogaster. By exploiting the genetic and molecular tools available toDrosophila researchers they have undertaken screens to identify genes required for pathway activity. They have also undertaken detailed, in depth analysis of a subset of these molecules in their normal developmental context. As such the scientists are improving understanding of this important signalling cascade to allow people to better diagnose and treat the diseases it can produce.
  • Cellular subtype identity in the pancreas

    2006 Mansouri, Ahmed
    A minor part of the pancreas is responsible for the secretion of hormones, such as insulin, to regulate the bloodsugar level. The mouse is used as an animal model to identify factors that drive the cellular subtype identity of these different hormone-producing cells. Two transcription factors Arx and Pax4 are required for the proper and coordinated development of these cells.

2005

  • Germ Cell Development in Zebrafish

    2005 Raz, Erez
    Animals are made of two major cell types, somatic cells that are responsible for the development and survival of the organism (e.g. muscle cells, cells in the nervous system etc.) and germ cells that are responsible for the generation of a new organism in the next generation by forming sperm and eggs. Scientists at the MPI in Göttingen are studying the development of germ cells in zebrafish, a vertebrate model organism that offers numerous advantages for such studies. Importantly, zebrafish embryos develop outside the body of the mother and are translucent allowing us to easily observe the germ cells within the live animal. Moreover, in studying the development of the cells we can use a large number of genetic techniques such as reducing the level of specific proteins, expression of different genes in different positions in the embryo etc. The research focus of our group is the understanding of the molecular basis for early germ cell development and behavior as well as studying the interaction between somatic and germ cells. To this end we analyze the mechanisms that are responsible for the segregation of the somatic and germ cell populations and the mechanisms responsible for the migration of the cells towards the gonad, the organ in which they generate sperm and eggs. Using mutations affecting the development of somatic cells we can determine whether the somatic cells provide the germ cells with signals important for their development and conversely, we analyze the development of somatic cells in which germ cell development is blocked.
  • New law in light microscopy allows for unprecedented resolution

    2005 Hell, Stefan W.

    Light microscopy has continually played a key role in science, but diffraction has limited the imaging of details that are smaller than about half the wavelength of light. For the important contrast mode of fluorescence, which is crucial to modern cell and molecular biology, the diffraction barrier has now been broken. In spite of relying on focused visible light, stimulated emission depletion (STED) microscopy is not limited by diffraction. To date, current schemes of STED-microscopy have delivered 50 nm (1/12 of the wavelength) resolution on cell membranes.

2004

  • Molecular and cellular mechanisms of synaptic development and plasticity

    2004 Sigrist, Stephan
    Synapses are the places where neurons speak to each other, and changing synapses seemingly underlies information storage in the nervous system. The Max Planck group "Neuroplasticity" focuses on the cellular and molecular mechanisms of synapse assembly and plasticity, using neuromuscular synapses of Drosophila as a model system. Apart from combining genetic approaches typical for Drosophila with electrophysiological analysis we have developed protocols, which allow to follow identified synapses over extended time periods in the intact animal. The team of Stephan Sigrist particularly concentrate on the glutamate receptors which receive the acitivity signal from the presynaptic neuron. We find that new glutamate receptor fields form exclusively de novo and usually grow to their characteristic mature size within about 24 hours. The mobility of glutamate receptors at individual receptor fields was analyzed in photo-bleaching and photo-activation experiments. While mature receptor fields are stable because both glutamate receptor entry and exit are low, the entry of glutamate receptors directly controls receptor field growth. Consistently, we find that glutamate receptors are directly needed for postsynaptic assembly independent of their ionic conductance. The in vivo imaging is currently used to illuminate how pre- and postsynaptic site interact within synapse assembly as well as to study the interplay of glutamate receptor dynamics glutamate receptor binding partners and postsynaptic assembly. In this context, the working group find that the Drosophila glutamate receptor binding protein homologue surprisingly controls muscle cell guidance.
  • Vibrational energy transfer through molecular chains

    2004 Schwarzer, Dirk
    Intramolecular vibrational energy flow in bridged azulene-anthracene compounds is investigated by time-resolved spectroscopy. The bridges consist of molecular chains of the type (CH2)m with m ≤ 6 as well as (CH2OCH2)n (n = 1,2) and CH2SCH2. With a short laser pulse excited molecules are formed where the excess vibrational energy is localised initially at the azulene side. The vibrational energy transfer through the molecular bridge to the anthracene side is followed by probing the energy content of the azulene and/or the anthracene chromophore with a second delayed laser pulse. The corresponding time constants τIVR for short bridges increase with the chain length. For longer bridges consisting of more than 3 elements, however, τIVR is constant at around 4-5 ps. Comparison with molecular dynamics simulations suggests that the coupling of these chains to the two chromophores limits the rate of intramolecular vibrational energy transfer. Inside the bridges the energy transport is essentially ballistic and, therefore, τIVRis independent on the length.
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