Project description:The recent increase in extensively drug resistant bacterial pathogens and the associated increase of morbidity and mortality demonstrate the immediate need for new antibiotic backbones with novel mechanisms of action. Here, we report the development of the PepSAVI-MS pipeline for bioactive peptide discovery. This highly versatile platform employs bioinformatics, statistics, and mass spectrometry to identify bioactive peptide targets from complex biological samples. We validate the use of this platform through the successful identification of known bioactive peptides from a botanical species, Viola odorata. Using this pipeline, we have widened the known antimicrobial spectrum for V. odorata cyclotides, including antibacterial activity of cycloviolacin O2 against E. faecium and A. baumannii. We further demonstrate the broad applicability of the platform through the identification of novel anticancer activities for cycloviolacins by their cytotoxicity against ovarian, breast and prostate cancer cell lines.
Project description:This model was reconstructed from single-nucleus RNA-seq (snRNA-seq) data of human postmortem brain and curated using published metabolomics data from human iPSC-derived neurons and cerebrospinal fluid (CSF), together with gene expression data from the Human Protein Atlas. It more accurately simulates human neuronal metabolic flux in neurodegenerative conditions such as Alzheimer's disease (AD).