5 research outputs found
Proteome profiling illustrated by a large-scale fed-batch fermentation of Penicillium chrysogenum
Filamentous fungi are employed for the large-scale production of value-added products, including organic acids, enzymes, and antibiotics and bioprocess characterization is essential for production optimization but relies on empiricism-based strategies. Protein expression profiles in an industrial scale, 180Â h fed-batch fermentation of Penicillium chrysogenum are presented. The biomass of P. chrysogenum, as well as the specific penicillin V production rate and fungal morphology were monitored during fermentation to be compared with obtained protein profiles. Our results demonstrate a correlation between proteomics data and biomass concentration, morphological changes, and penicillin production
CAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns
Respiratory syncytial virus is a leading cause of morbidity and mortality in children, due in part to their distinct immune system, characterized by impaired induction of Th 1 immunity. Here we show application of cationic adjuvant formulation CAF08, a liposomal vaccine formulation tailored to induce Th 1 immunity in early life via synergistic engagement of Toll-like Receptor 7/8 and the C-type lectin receptor Mincle. We apply quantitative phosphoproteomics to human dendritic cells and reveal a role for Protein Kinase C-δ for enhanced Th1 cytokine production in neonatal dendritic cells and identify signaling events resulting in antigen cross-presentation. In a murine in vivo model a single immunization at birth with CAF08-adjuvanted RSV pre-fusion antigen protects newborn mice from RSV infection by induction of antigen-specific CD8(+) T-cells and Th1 cells. Overall, we describe a pediatric adjuvant formulation and characterize its mechanism of action providing a promising avenue for development of early life vaccines against RSV and other respiratory viral pathogens
Recommended from our members
Multisystem Analysis of Mycobacterium tuberculosis Reveals Kinase-Dependent Remodeling of the Pathogen-Environment Interface
ABSTRACT Tuberculosis is the leading killer among infectious diseases worldwide. Increasing multidrug resistance has prompted new approaches for tuberculosis drug development, including targeted inhibition of virulence determinants and of signaling cascades that control many downstream pathways. We used a multisystem approach to determine the effects of a potent small-molecule inhibitor of the essential Mycobacterium tuberculosis Ser/Thr protein kinases PknA and PknB. We observed differential levels of phosphorylation of many proteins and extensive changes in levels of gene expression, protein abundance, cell wall lipids, and intracellular metabolites. The patterns of these changes indicate regulation by PknA and PknB of several pathways required for cell growth, including ATP synthesis, DNA synthesis, and translation. These data also highlight effects on pathways for remodeling of the mycobacterial cell envelope via control of peptidoglycan turnover, lipid content, a SigE-mediated envelope stress response, transmembrane transport systems, and protein secretion systems. Integrated analysis of phosphoproteins, transcripts, proteins, and lipids identified an unexpected pathway whereby threonine phosphorylation of the essential response regulator MtrA decreases its DNA binding activity. Inhibition of this phosphorylation is linked to decreased expression of genes for peptidoglycan turnover, and of genes for mycolyl transferases, with concomitant changes in mycolates and glycolipids in the cell envelope. These findings reveal novel roles for PknA and PknB in regulating multiple essential cell functions and confirm that these kinases are potentially valuable targets for new antituberculosis drugs. In addition, the data from these linked multisystems provide a valuable resource for future targeted investigations into the pathways regulated by these kinases in the M. tuberculosis cell
Combining light microscopy, dielectric spectroscopy, MALDI intact cell mass spectrometry, FTIR spectromicroscopy and multivariate data mining for morphological and physiological bioprocess characterization of filamentous organisms
Commissioning of the hypertriton binding energy measurement at MAMI
A high-precision hypernuclear experiment has been commissioned at the Mainz Microtron (MAMI) to determine the hypertriton Λ binding energy via decay-pion spectroscopy. The method has been successfully pioneered with 4ΛH studies in the last decade. The experiment makes use of a novel high luminosity lithium target with a length of 45mm while being only 0.75mm thick to keep momentum smearing of the decay pions low. The target-to-beam alignment as well as the observation of the deposited heat is achieved with a newly developed thermal imaging system. Together with a precise beam energy determination via the undulator light interference method a recalibration of the magnetic spectrometers will be done to obtain a statistical and systematic error of about 20 keV. The experiment started in the summer of 2022 and initial optimization studies for luminosity and data quality are presented