ORCID Profile
0000-0002-5313-2176
Current Organisation
Freie Universität Berlin
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Publisher: Microbiology Society
Date: 10-2017
DOI: 10.1099/JGV.0.000919
Publisher: American Society for Microbiology
Date: 15-05-2010
DOI: 10.1128/JVI.02469-09
Abstract: The patterns and dynamics of evolution in acutely infecting viruses within in idual hosts are largely unknown. To this end, we investigated the intrahost variation of canine influenza virus (CIV) during the course of experimental infections in naïve and partially immune dogs and in naturally infected dogs. Tracing sequence ersity in the gene encoding domain 1 of the hemagglutinin (HA1) protein over the time course of infection provided information on the patterns and processes of intrahost viral evolution and revealed some of the effects of partial host immunity. Viral populations s led on any given day were generally characterized by mean pairwise genetic ersities between 0.1 and 0.2% and by mutational spectra that changed considerably on different days. Some observed mutations may have affected antigenicity or host range, including reversions of CIV host-associated mutations. Patterns of sequence ersity differed between naïve and vaccinated dogs, with some presumably antigenic mutations transiently reaching high frequency in the latter. CIV populations are therefore characterized by the rapid generation and clearance of genetic ersity. Potentially advantageous mutations arise readily during the course of single infections and may give rise to antigenic escape or host range variants.
Publisher: Cold Spring Harbor Laboratory
Date: 19-08-2020
DOI: 10.1101/2020.08.18.255380
Abstract: Solute-binding proteins (SBPs) have evolved to balance the demands of ligand affinity, thermostability and conformational change to accomplish erse functions in small molecule transport, sensing and chemotaxis. Although the ligand-induced conformational changes that occur in SBPs make them useful components in biosensors, they are challenging targets for protein engineering and design. Here we have engineered a D-alanine-specific SBP into a fluorescent biosensor with specificity for the signaling molecule D-serine (D-serFS). This was achieved through binding site and remote mutations that improved affinity ( K D = 6.7 ± 0.5 μM), specificity (40-fold increase vs. glycine), thermostability (Tm = 79 °C) and dynamic range (~14%). This sensor allowed measurement of physiologically relevant changes in D-serine concentration using two-photon excitation fluorescence microscopy in rat brain hippoc al slices. This work illustrates the functional trade-offs between protein dynamics, ligand affinity and thermostability, and how these must be balanced to achieve desirable activities in the engineering of complex, dynamic proteins.
Publisher: Springer Science and Business Media LLC
Date: 30-07-2018
DOI: 10.1038/S41589-018-0108-2
Abstract: Fluorescent sensors are an essential part of the experimental toolbox of the life sciences, where they are used ubiquitously to visualize intra- and extracellular signaling. In the brain, optical neurotransmitter sensors can shed light on temporal and spatial aspects of signal transmission by directly observing, for instance, neurotransmitter release and spread. Here we report the development and application of the first optical sensor for the amino acid glycine, which is both an inhibitory neurotransmitter and a co-agonist of the N-methyl-D-aspartate receptors (NMDARs) involved in synaptic plasticity. Computational design of a glycine-specific binding protein allowed us to produce the optical glycine FRET sensor (GlyFS), which can be used with single and two-photon excitation fluorescence microscopy. We took advantage of this newly developed sensor to test predictions about the uneven spatial distribution of glycine in extracellular space and to demonstrate that extracellular glycine levels are controlled by plasticity-inducing stimuli.
Publisher: American Society for Microbiology
Date: 06-01-2019
DOI: 10.1128/JVI.01625-19
Abstract: With the cessation of vaccination against smallpox and its assumed cross-protectivity against other OPV infections, waning immunity could open up new niches for related poxviruses. Therefore, the identification of virulence mechanisms in CPXV is of general interest. Here, we aimed to identify virulence markers in an experimental rodent CPXV infection model using bacterial artificial chromosome (BAC)-based virus recombineering. We focused our work on the recent zoonotic CPXV isolate RatPox09, which is highly pathogenic in Wistar rats, unlike the avirulent BR reference strain. In several animal studies, we were able to identify a novel set of CPXV virulence genes. Two of the identified virulence genes, encoding a putative BTB/POZ protein (CPXVD7L) and a B22R-family protein (CPXV7tGP), respectively, have not yet been described to be involved in CPXV virulence. Our results also show that single genes can significantly affect virulence, thus facilitating adaptation to other hosts.
Publisher: Wiley
Date: 20-03-2012
DOI: 10.1111/J.2042-3306.2012.00554.X
Abstract: To date, no information is available on the true biological elimination half-life (T(1/2) ) of cardiac troponin I (cTnI) in the equine species. Such data are required to better evaluate the optimal time to acquire the cTnI s le following acute myocardial injury. To determine the T(1/2) of equine cTnI. Four healthy ponies received i.v. injections of recombinant equine cTnI. Plasma cTnI concentrations were measured with a point-of-care cTnI analyser at multiple time points after injection. Standard pharmacokinetic analysis was performed to establish the T(1/2) of cTnI. The average T(1/2) of cTnI was determined to be 0.47 h using a single rate elimination model. The elimination of recombinant equine cTnI following i.v. administration is very rapid. Establishing the T(1/2 ) of troponin provides critical information in understanding the clinical application of this cardiac biomarker in equine practice.
Publisher: Wiley
Date: 14-08-2012
Publisher: Elsevier BV
Date: 11-2013
Publisher: Springer Science and Business Media LLC
Date: 13-09-2021
DOI: 10.1038/S41586-021-03995-1
Abstract: Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs.
No related grants have been discovered for Nikolaus Osterrieder.