Biowissenschaften
Refine
Year of publication
Document Type
- Article (776)
- Doctoral Thesis (574)
- Book (48)
- Contribution to a Periodical (37)
- Diploma Thesis (10)
- Conference Proceeding (9)
- Preprint (5)
- diplomthesis (4)
- Review (4)
- Report (3)
Has Fulltext
- yes (1472)
Is part of the Bibliography
- no (1472)
Keywords
- aging (9)
- Podospora anserina (8)
- autophagy (8)
- Archaea (7)
- mitochondria (7)
- Westafrika (6)
- heat stress (6)
- phylogeny (6)
- Cell biology (5)
- Mitochondria (5)
Institute
- Biowissenschaften (1472)
- Senckenbergische Naturforschende Gesellschaft (109)
- Präsidium (100)
- Biodiversität und Klima Forschungszentrum (BiK-F) (97)
- Institut für Ökologie, Evolution und Diversität (85)
- Medizin (81)
- Exzellenzcluster Makromolekulare Komplexe (66)
- Biochemie und Chemie (56)
- Pharmazie (24)
- Informatik (21)
Determining the structure and mechanisms of all individual functional modules of cells at high molecular detail has often been seen as equal to understanding how cells work. Recent technical advances have led to a flush of high-resolution structures of various macromolecular machines, but despite this wealth of detailed information, our understanding of cellular function remains incomplete. Here, we discuss present-day limitations of structural biology and highlight novel technologies that may enable us to analyze molecular functions directly inside cells. We predict that the progression toward structural cell biology will involve a shift toward conceptualizing a 4D virtual reality of cells using digital twins. These will capture cellular segments in a highly enriched molecular detail, include dynamic changes, and facilitate simulations of molecular processes, leading to novel and experimentally testable predictions. Transferring biological questions into algorithms that learn from the existing wealth of data and explore novel solutions may ultimately unveil how cells work.
Nisin-producing Lactococcus lactis strains show a high degree of resistance to the action of nisin, which is based upon expression of the self-protection (immunity) genes nisI, nisF, nisE, and nisG. Different combinations of nisin immunity genes were integrated into the chromosome of a nisin-sensitive Bacillus subtilis host strain under the control of an inducible promoter. For the recipient strain, the highest level of acquired nisin tolerance was achieved after coordinated expression of all four nisin immunity genes. But either the lipoprotein NisI or the ABC transporter-homologous system NisFEG, respectively, were also able to protect the Bacillus host cells. The acquired immunity was specific to nisin and provided no tolerance to subtilin, a closely related lantibiotic. Quantitative in vivo peptide release assays demonstrated that NisFEG diminished the quantity of cell-associated nisin, providing evidence that one role of NisFEG is to transport nisin from the membrane into the extracellular space. NisI solubilized from B. subtilis membrane vesicles and recombinant hexahistidine-tagged NisI from Escherichia coli interacted specifically with nisin and not with subtilin. This suggests a function of NisI as a nisin-intercepting protein.
Analysis of whole cell lipid extracts of bacteria by means of ultra-performance (UP)LC-MS allows a comprehensive determination of the lipid molecular species present in the respective organism. The data allow conclusions on its metabolic potential as well as the creation of lipid profiles, which visualize the organism's response to changes in internal and external conditions. Herein, we describe: i) a fast reversed phase UPLC-ESI-MS method suitable for detection and determination of individual lipids from whole cell lipid extracts of all polarities ranging from monoacylglycerophosphoethanolamines to TGs; ii) the first overview of a wide range of lipid molecular species in vegetative Myxococcus xanthus DK1622 cells; iii) changes in their relative composition in selected mutants impaired in the biosynthesis of α-hydroxylated FAs, sphingolipids, and ether lipids; and iv) the first report of ceramide phosphoinositols in M. xanthus, a lipid species previously found only in eukaryotes.
The TolC-like protein HgdD of the filamentous, heterocyst-forming cyanobacterium Anabaena sp. PCC 7120 is part of multiple three-component "AB-D" systems spanning the inner and outer membranes and is involved in secretion of various compounds, including lipids, metabolites, antibiotics, and proteins. Several components of HgdD-dependent tripartite transport systems have been identified, but the diversity of inner membrane energizing systems is still unknown. Here we identified six putative resistance-nodulation-cell division (RND) type factors. Four of them are expressed during late exponential and stationary growth phase under normal growth conditions, whereas the other two are induced upon incubation with erythromycin or ethidium bromide. The constitutively expressed RND component Alr4267 has an atypical predicted topology, and a mutant strain (I-alr4267) shows a reduction in the content of monogalactosyldiacylglycerol as well as an altered filament shape. An insertion mutant of the ethidium bromide-induced all7631 did not show any significant phenotypic alteration under the conditions tested. Mutants of the constitutively expressed all3143 and alr1656 exhibited a Fox(-) phenotype. The phenotype of the insertion mutant I-all3143 parallels that of the I-hgdD mutant with respect to antibiotic sensitivity, lipid profile, and ethidium efflux. In addition, expression of the RND genes all3143 and all3144 partially complements the capability of Escherichia coli ΔacrAB to transport ethidium. We postulate that the RND transporter All3143 and the predicted membrane fusion protein All3144, as homologs of E. coli AcrB and AcrA, respectively, are major players for antibiotic resistance in Anabaena sp. PCC 7120.
The role of Apelin signaling and endocardial protrusions during cardiac development in zebrafish
(2023)
During cardiac development, cardiomyocytes (CMs) are delaminated from the compact muscle wall to increase the muscle mass of the heart. This process is also known as cardiac trabeculation. It has been shown that growth factors produced by endocardial cells (EdCs) are required for myocardial morphogenesis and growth. In particular, Neuregulin produced by EdCs promotes myocardial trabeculation. The deficiency of Neuregulin signaling leads to hypotrabeculation. Endocardial protrusions project from the endocardium to the myocardium are also essential for the trabeculae onset. Yet current studies only introduce the function of endocardial sprouts descriptively. This article first reports the mechanisms of endocardial sprouting during myocardial trabeculation. By living imaging, we first demonstrate that EdCs interact with CMs through membrane protrusions in zebrafish embryos. More interestingly, these protrusions stay in close contact with their target CMs in spite of the cardiac contraction. We utilize loss-of-function strategies to report the importance of myocardial apelin, which induces endocardial protrusion formation. Zebrafish lacking Apelin signaling exhibit defects in endocardial protrusion formation as well as excessive deposition of cardiac jelly and hypotrabeculation. Notably, we also present data that blocking protrusion formation in endocardial cells phenocopies the trabeculation defects in apelin mutants. Mechanistically, endocardial-derived Neuregulin requires Apelin signaling mediated endocardial protrusions, and Neuregulin dependent pERK expression is attenuated in the condition of reduced endocardial protrusion formation. Together, our data suggest that endocardial-myocardial communication through endocardial protrusions acts as an underlying principle allowing myocardial growth.
The production of bulk chemicals mostly depends on exhausting petroleum sources and leads to emission of greenhouse gases. Within the last decades the urgent need for alternative sources has increased and the development of bio-based processes received new attention. To avoid the competition between the use of sugars as food or fuel, other feedstocks with high availability and low cost are needed, which brought acetogenic bacteria into focus. This group of anaerobic organisms uses mixtures of CO2, CO and H2 for the production of mostly acetate and ethanol. Also methanol, a cheap and abundant bulk chemical produced from methane, is a suitable substrate for acetogenic bacteria. In methylotrophic acetogens the methyl group is transferred to the Wood-Ljungdahl pathway, a pathway to reduce CO2 to acetate via a series of C1-intermediates bound to tetrahydrofolic acid. Here we describe the biochemistry and bioenergetics of methanol conversion in the biotechnologically interesting group of anaerobic, acetogenic bacteria. Further, the bioenergetics of biochemical production from methanol is discussed.
Filamentous enzymes have been found in all domains of life, but the advantage of filamentation is often elusive1. Some anaerobic, autotrophic bacteria have an unusual filamentous enzyme for CO2 fixation—hydrogen-dependent CO2 reductase (HDCR)2,3—which directly converts H2 and CO2 into formic acid. HDCR reduces CO2 with a higher activity than any other known biological or chemical catalyst4,5, and it has therefore gained considerable interest in two areas of global relevance: hydrogen storage and combating climate change by capturing atmospheric CO2. However, the mechanistic basis of the high catalytic turnover rate of HDCR has remained unknown. Here we use cryo-electron microscopy to reveal the structure of a short HDCR filament from the acetogenic bacterium Thermoanaerobacter kivui. The minimum repeating unit is a hexamer that consists of a formate dehydrogenase (FdhF) and two hydrogenases (HydA2) bound around a central core of hydrogenase Fe-S subunits, one HycB3 and two HycB4. These small bacterial polyferredoxin-like proteins oligomerize through their C-terminal helices to form the backbone of the filament. By combining structure-directed mutagenesis with enzymatic analysis, we show that filamentation and rapid electron transfer through the filament enhance the activity of HDCR. To investigate the structure of HDCR in situ, we imaged T. kivui cells with cryo-electron tomography and found that HDCR filaments bundle into large ring-shaped superstructures attached to the plasma membrane. This supramolecular organization may further enhance the stability and connectivity of HDCR to form a specialized metabolic subcompartment within the cell.
Hydrogen is a promising fuel in a carbon-neutral economy, and many efforts are currently undertaken to produce hydrogen. One of the challenges is to store and transport the highly explosive gas in a safe and easy way. One option that is intensively analyzed by chemists and biologists is the conversion of hydrogen and CO2 to formic acid, the liquid organic hydrogen carrier. Here, we demonstrate for the first time that a bio-based system, using Acetobacterium woodii as the biocatalyst, allows multiple cycles of bi-directional hydrogenation of CO2 to formic acid in one bioreactor. The process was kept running over 2 weeks producing and oxidizing 330 mM formic acid in total. Unwanted side-product formation of acetic acid was prevented through metabolic engineering of the organism. The demonstrated process design can be considered as a future “bio-battery” for the reversible storage of electrons in the form of H2 in formic acid, a versatile compound.
In our rapidly changing world, land use has been recognized as having one of the strongest impacts on species and genetic diversity. The present state of temperate forests in Europe is a product of decisions made by former and current management and policy actions, rather than natural factors. Alterations of crown projection areas, structural complexity of the forest stand caused by thinning and cuttings, and changes in tree species composition caused by regeneration or plantings not only affect forest interior buffering against warming, but also the understorey light environment and nutrient availability. Ultimately, current silvicultural management practices have deep impact on the forest ecosystems, microenvironmental changes and forest floor understorey herbs. In response to environmental changes, plants rely on genetically heritable phenotypic variation, an important level of variation in the population, as it is prerequisite for adaptation. However, until now most studies on plant adaptation to land use focus on grassland management. Yet, studies on the adaptation of forest understorey herbs to forest management have been absent so far. This is important because understanding adaptation of understorey herbs is crucial for biodiversity conservation, forest restoration, and climate change mitigation. Studying current adaptation of understorey herbs to forest management yields insights into the evolutionary consequences of management practices, which could be employed to improve sustainable use of forest habitat.
In sum, my conducted experiments complement each other well and managed to fill in research gaps on the topic of genetically heritable phenotypic variation in understorey herbs and how it is affected by forest management and related microenvironmental variables. I showed that forest management has direct evolutionary consequences on the genetic basis of understorey herbs, but also indirectly through the microenvironment. Furthermore, I revealed that local adaptation and phenotypic plasticity of understorey herbs to forest structural attributes act along continuous gradients. And lastly, I highlighted the important role of intra-individual variation by revealing plastic responses to drought and shading, urging researchers to not ignore this important level of trait variation. Ultimately, understorey herbs in temperate forests employ phenotypic plasticity as a flexible strategy to adapt to varying environmental conditions. By adjusting their leaf characteristics, reproductive investment, and phenology, they can optimize their fitness and survival in response to changes in light availability, resource availability, and seasonal cues. The anthropogenic impact on temperate forests and understorey herbs will continue and likely increase in the future. This should urge foresters to adapt their silvicultural management decisions towards the long-term preservation of genetic diversity and, through this, the evolvability and adaptability of forest understorey herbs and associated organisms. Based on the results shown in my dissertation, variation in forest management regimes and types could be beneficial for promoting genetic diversity within several species of forest understorey herbs. Lastly, in the face of future climatic changes, the mechanisms by which plants can cope with increasing stressful environmental conditions might very well rely heavily on intra-individual variation, providing the necessary rapid plastic adjustment to changing microclimatic conditions within populations and thus increase climate change resilience.
Streams and rivers are characterised by the presence of various chemicals of emerging concern (CECs), including pesticides, pharmaceuticals, personal care products, and industrial chemicals. While these chemicals are found usually only in low (ng/L) concentrations, they might still harm aquatic life and disrupt the ecological balance of aquatic ecosystems due to their high ecotoxicological potency. Environmental risk assessments that account for the complexity of exposures are needed in order to evaluate the toxic pressure of these chemicals, which also provide suggestions for risk mitigation and management, if necessary. Currently, most studies on the co-occurrence and environmental impacts of CECs are conducted in countries of the Global North, leaving massive knowledge gaps in countries of the Global South.
In this study, we implement a multi-scenario risk assessment strategy to improve the assessment of both the exposure and hazard components in the chemical risk assessment process. Our strategy incorporates a systematic consideration and weighting of CECs that were not detected, as well as an evaluation of the uncertainties associated with Quantitative Structure-Activity Relationships (QSARs) predictions for chronic ecotoxicity. Furthermore, we present a novel approach to identifying mixture risk drivers. To expand our knowledge beyond well-studied aquatic ecosystems, we applied this multi-scenario strategy to the River Aconcagua basin of Central Chile. The analysis revealed that the concentrations of CECs exceeded acceptable risk thresholds for selected organism groups and the most vulnerable taxonomic groups. Streams flowing through agricultural areas and sites near the river mouth exhibited the highest risks. Notably, the eight risk drivers among the 153 co-occurring chemicals accounted for 66-92% of the observed risks in the river basin. Six of them are pesticides and pharmaceuticals, chemical classes known for their high biological activity in specific target organisms.