Chaperone vermitteln die Aufnahme bakterieller AB-Toxine in Säugerzellen(S. 374)
Holger Barth, Katharina Ernst
Bacterial ADP-ribosylating toxins (ADP-RTs) cause severe diseases e. g. whooping cough or enterotoxicity by modifying their substrates in the cytosol leading to cellular dysfunction and clinical symptoms. We discovered that for cytosolic uptake of ADP-RTs the activity of host cell factors Hsp90, Hsp70, cyclophilins and FK506-binding proteins is required. Pharmacological targeting of these factors might be a starting point for novel therapeutic strategies against diseases caused by ADP-RTs.
Regulation der Proteostase – ein Fokus auf das Ubiquitin-Proteasomen-System(S. 379)
Frédéric Ebstein, Elke Krüger
Regulated proteolysis by the ubiquitin proteasome system (UPS) is vital for cells to preserve protein homeostasis (proteostasis). Proteotoxic stress by radical production can severely challenge proteostasis closely interconnecting redox with protein homeostasis. To counteract proteo - toxicity the capacity of the UPS is adjusted by differential expression of UPS factors and proteasome isoforms. Faulty regulation or proteasome impairment that cause an interferon response are hallmarks of many diseases and will be discussed.
Die Kontrolle zyklischer Nukleotide mittels Licht(S. 384)
Andreas Möglich, Robert Stabel
Sensory photoreceptors underpin diverse adaptive responses in nature and serve as genetically encoded, light-gated actuators in optogenetics. Photoactivated nucleotide cyclases (PACs) enable light-dependent control over the formation of cyclic nucleotides (cNMPs). Conversely, the engineered, red-light-activated phosphodiesterase LAPD mediates the hydrolytic breakdown of cNMPs. In combination, PACs and LAPD hence unlock precise and graded control over intracellular cNMPs and associated processes.
Kabelbakterien ermöglichen neue geochemische Prozesse(S. 388)
Rainer Meckenstock, HUbert Müller
The discovery of long-distance electron transfer by cable bacteria over centimetre distances was ground-breaking in environmental microbiology in recent years. Cable bacteria transfer electrons between anodic sulphide oxidation and cathodic oxygen reduction – the only example known so far for an organism separating redox half-reactions into different locations. The discovery of cable bacteria in contaminated aquifers pronounces their importance in different habitats.
Proteasen in der Alzheimer-Forschung – Freund oder Feind?(S. 391)
Johanna Tüshaus, Tobias Brummer, Stephan Müller, Stefan Lichtenthaler
Proteases have a central role in Alzheimer’s disease, but their use as drug targets is difficult as they have a broad substrate spectrum. Using the example of the Alzheimer α- and β-secretase, this article demonstrates how modern mass spectrometry-based methods allow to systematically identify the substrates of membrane-bound proteases and thereby determine the physiological functions as well as the suitability of these proteases as drug targets for Alzheimer’s disease and other disorders.
Mikrofluidik – großes Potenzial in kleinen Tropfen(S. 394)
J. Michael Köhler, Jialan Cao, Tim Schüler
The technique of micro segmented flow is well applicable for the investigation of soil microorganisms. It supplies highly resolved dose/ response functions for whole microbial communities as well as for single strains. In addition, it can be used in the search for microbial strains with special tolerance features, for example for enhanced concentrations of cobalt and nickel. Such strains have been found in soil samples from the surface of ancient copper mining areas and metal-contaminated soils from archaeological excavations.
At-line Monitoring von Zellkulturprozessen mittels Massenspektrometrie(S. 399)
Sebastian Schwamb, Philipp Wiedemann
Perfusion becomes a reasonable alternative to traditional batch or fed-batch processes, partly due to the increasing availability of suitable re-usable or single-use equipment. High cell densities and long duration of perfusion processes require reliable process control. Amongst others, monitoring of cell stress becomes important. Intact cell MALDITOF mass spectrometry (ICM-MS) biotyping is described here as a robust at-line monitoring method of cell stress in perfusion cell culture.
Hypoxie – Wenn weniger (Sauerstoff) mehr (Stammzellen) macht(S. 404)
Cornelia Kasper, Dominik Egger
The standard cell culture oxygen concentration of 21 percent O2 does not represent the physiologic environment of stem cells. Indeed, hypoxic (< 21 percent O2) conditions heavily affect cellular processes such as growth, apoptosis and energy metabolism. In the context of clinical trials a fast ex vivo expansion of stem cells while maintaining their stem cell properties is crucial. However, maintaining hypoxic conditions during cultivation is challenging and puts high requirements on laboratory equipment.
Modulation von Proteinfunktion mit Alpaka-Nanobodies in lebenden Zellen(S. 408)
Florian Ingo Schmidt
New genetic tools allow the disruption of every single gene. Yet, we only have limited tools to target biological processes at the protein level. Alpaca nanobodies can modulate and visualize protein function in living cells. This article describes a functional screening approach that identifies nanobodies based on the phenotype they elicit when expressed in the cytosol. In principle, this approach will allow the identification of specific activators and inhibitors of any biological pathway.
Anwendungen & Produkte
3D-Zellkultursystem für die Nachbildung biologischer Barrieren(S. 422)
Stefanie Büsch, Srinivasan Kokatam, Jenny Schröder
In tissues, cells are spatially organized in three dimensions and interact with neighbouring cells and the extracellular matrix (ECM). This can be mimicked in vitro with a new 3D cell culture system that is using the most abundant ECM molecule to embed cells, collagen type I. It allows cells to grow in in vivo-like structures. This article describes how human tissue barriers like the bronchial epithelium, cornea or blood-brain-barrier can be modelled.
Peptidliganden zur Aufreinigung kamelider Schwere-Ketten-Antikörper(S. 424)
Matthias Paschke, Veit Althoff
Highly specific peptides that bind a given target protein are useful ligands for the affinity purification of such proteins from complex biological matrices. The capability to provide this kind of peptidic ligands for the affinity purification of virtually any protein can simplify and enhance the downstream process development. The general applicability, scalability, and comparatively low costs of peptidic ligands are key features for their application in downstream purification processes.
Eine vollständig reversible, nicht-magnetische Zellisolation(S. 427)
Marie-Luise Kiene, Franziska Leonhardt, Lisa Breithaupt, Michael Tietzel, Herbert Stadler
A new automated bench top instrument quantitatively selects cells of interest in high yields and purity from whole blood or other blood preparations using the traceless affinity cell selection technology (TACS). This enables a fully reversible capture and release of target cells. TACS uses immune affinity chromatography based on CD-specific Fab-fragments which delivers label-free, non-activated target cells in a standardized manner of reproducible quality.
Zellen beim Atmen beobachten – Stoffwechselforschung in der Mikroplatte(S. 430)
Dysregulation of cellular energy metabolism is a common factor in a variety of disorders such as diabetes and obesity as well as cancer. New technologies assess mitochondrial function via extracellular acidification (ECA) and oxygen consumption rate (OCR). These can be determined at physiological or stroke-mimicking oxygen conditions.
Enzymatische Reaktionskaskaden – „Fernbeziehungen“ und „Wohngemeinschaften“(S. 468)
Kara Selin, Jörg H. Schrittwieser
Multi-enzymatic cascade reactions enable the (re)design of synthetic routes via efficient multi-step biotransformations. Interestingly, enzy -matic cascades can profit both from spatial separation (e. g. by compart-mentalization) and from co-localization of the involved enzymes (e. g. by co-immobilization). In this overview article we discuss recent literature examples illustrating the advantages and limitations of both these strategies.
Die mikrobielle Elektrosynthese von Methan(S. 471)
Dirk Holtmann, Florian Mayer, Franziska Enzmann, Antonio Martinez Lopez
Methane is not only a potent greenhouse gas but also a modern biofuel, which is produced mainly by biological methanation in biogas plants. Here we describe an alternative process of methane production, called „microbial electrosynthesis“. This process has the potential to reduce CO2 emissions and to convert electrical excess current or renewable energies into methane.