Trypanothion – Wunderwaffe und Achillesferse der Trypanosomatiden(S. 344)
Kathrin Diederich, R. Luise Krauth-Siegel
Trypanosomatids are protozoan parasites with a unique trypanothionebased thiol redox metabolism. Mediated by the small oxidoreductase tryparedoxin, trypanothione is the universal electron donor for the biosynthesis of DNA precursors, reduction of methionine sulfoxides as well as detoxification of hydroperoxides by distinct thiol peroxidases. The fact that nearly all enzymes involved are essential renders the pathway attractive for drug development approaches against these parasites.
Un-/Gewöhnliche Reaktionen im mikrobiellen Metabolismus(S. 348)
Ivan A. Berg
The diversity of microbial metabolism has significantly expanded in the last years by the discovery of several novel central metabolic pathways in different groups of prokaryotes. These novel pathways use a number of unusual intermediates, whose participation in the central metabolism was not anticipated. This fact reflects a bias in our choice of model organisms rather than a limited importance of discovered pathways/compounds in natural ecosystems. Metabolisms that we regard as unusual may actually represent mainstream processes in natural ecosystems.
Die Rolle humanspezifischer Gene in der Gehirnentwicklung und -evolution(S. 352)
Wieland B. Huttner, Michael Heide, Marta Florio
Only about five percent of our genome contains human-specific sequences. These sequences arose mostly from segmental duplications during human evolution and include genes that are unique to the human lineage. Although these genes are currently not well characterised, they may be potential key players in the development of human-specific traits, like an expanded neocortex. Here, we present an overview of the role of human-specific genes during development and evolution of the embryo - nic brain, with a focus on one of these genes, ARHGAP11B (Rho GTPase Activating Protein 11B).
Chromosom in Schleifen: SMC-Komplexe als molekulare Kabelbinder?(S. 356)
Larissa Wilhelm, Stephan Gruber
Chromosome compaction is an essential prerequisite for the faithful segregation of chromosomes during cell division. SMC proteins promote the compaction and resolution of sister DNA molecules. They form ring-like structures that are thought to tie selected segments of chromosomes together. The underlying molecular mechanisms, however, are still poorly understood. Insights gained for the bacterial ancestor of SMC provide an excellent basis for our general understanding of these highly conserved molecular machines.
AMP-Modifikationen als Strategien bakterieller Krankheitserreger(S. 359)
Bacterial pathogens have evolved with enzyme activities that may hijack intracellular signaling of mammalian cells to establish an infection. Of particular interest is a novel posttranslational modification referred to as adenylylation: An adenosine monophosphate group is covalently transferred to a mammalian target protein. Here, I discuss the consequences of adenylylation and its related modifications by Fic enzymes. Also, I comment on potential applications for protein labeling.
Quorum quenching – Störenfriede zwischenbakterieller Beziehungen(S. 362)
Nancy Weiland-Bräuer, Ruth A. Schmitz-Streit
Most bacteria are able to grow in biofilms in which they effectively resist antimicrobial agents. This leads to a general problem, since traditional treatments of bacteria and prevention strategies become mostly ineffective. Novel strategies for biofilm inhibition are thus urgently required. Compounds interfering with cell-cell communication (quorum sensing) crucial for biofilm formation are promising targets for alternative strategies. Here, we report on a recently established assay enabling identification of quorum quenching compounds from environmental samples.
Reversibel schaltbare fluoreszierende Proteine für die Superauflösung(S. 365)
Martin Andresen, Nickels Jensen, Stefan Jakobs
Super-resolution microscopy, or nanoscopy, enables the visualization of cellular structures inaccessible to conventional light microscopy. RESOLFT nanoscopy is especially suitable for the imaging of living cells. It requires fluorescent proteins (RSFPs) that can be repeatedly switched between a fluorescent and a non-fluorescent state by light. We have analyzed the molecular switching mechanisms and generated a family of RSFPs specifically tailored for live cell RESOLFT nanoscopy.
Rho-Signalgebung in der Tumorentstehung und -progression(S. 369)
Bettina Noll, Janina Hendrick, Monilola Olayioye
Metastatic cancers are characterized by uncontrolled cell proliferation and tissue invasion, processes controlled by small Rho GTPases, the activation of which is regulated by GEF and GAP proteins. Deleted in liver cancer (DLC) proteins are such Rho regulators that are downregulated in different types of cancer. Using proteomic approaches, genetically encoded biosensors and high resolution microscopy, our lab studies how the DLC proteins control cellular Rho activity patterns in time and space.
Synthetische subzelluläre Kompartimente in eukaryotischen Zellen(S. 374)
Mara Reifenrath, Joanna Tripp, Mislav Oreb, Eckhard Boles
Genetic engineering of metabolic pathways for biotechnological purposes is often hampered by factors like slow diffusion rates, competing pathways or secretion of intermediates. To bypass these limitations, compartimentalization of enzymatic reactions is a promising approach. For this, enzymes can either be arranged in complexes or they can be isolated in coated subcellular compartments. We are developing new concepts to assemble various enzymes in protein supercomplexes and to relocate metabolic pathways into synthetic organelles.
Aptamer-vermitteltes drug delivery(S. 378)
Eileen Magbanua, Ulrich Hahn
Aptamers are multifunctional tools relatively easy to generate and modify thus allowing a broad application spectrum. Highly specific for tumor markers or receptors aptamers are able to discriminate between healthy and malignant cells and furthermore may serve as vehicles for directed drug or therapeutic agents’ delivery.
Anwendungen & Produkte
Automatisierte Mikroskopie und Bildanalyse der zellulären Lipidspeicherung(S. 392)
Michael Werthebach, Joel Mailliet, Mathias Beller
The storage and remobilization of lipids as a reservoir for energy and metabolic building blocks is a central feature of organisms throughout all kingdoms of life. Surprisingly, little is known about lipid droplets (LDs), the organelles responsible for lipid storage on a cellular level. By the use of an automated microscope system, we here present different fluorescence based approaches to analyze the dynamics as well as the effectors of LD morphology and subcellular positioning.
3D-Migrationsassays im Hochdurchsatz(S. 395)
Brad Larson, Leonie Rieger, Hubert Tseng, Glauco R. Souza, Aleksandra Velkova-Krei
Migration assays are a common tool to screen toxic effects of compounds. However, assays using monolayer cell cultures may not entirely represent a native in vivo environment and may result in misinterpretation of compound toxicity. Magnetic 3D bioprinting in combination with automated kinetic imaging provides an easy and robust high-throughput screening approach of compound effects on cell migration in a 3D environment.
NanoBRET – ein neues Nachweisverfahren für die GPCR-Ligandenbindung(S. 398)
A number of assay techniques are currently used to study ligand binding to G protein-coupled receptors (GPCRs) in living cells. In contrast to FRET, BRET does only need the addition of a suitable substrate to generate light/energy which then excites the fluorescent binding partner. This article describes the newly developed NanoBRETTM method for monitoring ligand binding to GPCRs in live cells using a microplate reader. Saturation and competition binding experiments are shown.
Enzymatische Depolymerisation von Lignin mittels immobilisierter Laccase(S. 426)
Annika Jahn, Doreen Steffien, Martin Bertau
Lignin is a major component of plant material and is the most abundant renewable source of aromatic polymer in nature . At present it is typically treated as “waste” in paper and biofuel production. A promising alternative is the use of lignin as feedstock for aromatic base chemicals. The aim of the work was to provide access to this class of compounds by means of depolymerising lignin. Laccase immobilisates turned to be particular efficient biocatalysts for this purpose.