Efficient methods for diversifying genes of interest (GOIs) are essential in protein engineering. For example, OrthoRep, a yeast-based orthogonal DNA replication system that achieves the rapid in vivo diversification of GOIs encoded on a cytosolic plasmid (p1), has been successfully used to drive numerous protein engineering campaigns. However, OrthoRep-based GOI evolution has almost always started from single GOI sequences, limiting the number of locations on a fitness landscape from where evolutionary search begins.
View Article and Find Full Text PDFWhen nature evolves a gene over eons at scale, it produces a diversity of homologous sequences with patterns of conservation and change that contain rich structural, functional, and historical information about the gene. However, natural gene diversity accumulates slowly and likely excludes large regions of functional sequence space, limiting the information that is encoded and extractable. We introduce upgraded orthogonal DNA replication (OrthoRep) systems that radically accelerate the evolution of chosen genes under selection in yeast.
View Article and Find Full Text PDFChemerin is a distant member of the cystatin protein family, initially discovered as a chemotactic factor and subsequently also reported to act as adipokine and angiogenetic factor. The biological activity of chemerin is regulated at different levels, such as gene expression, protein processing and interaction with both signaling and nonsignaling receptors. Chemerin is mostly produced by stromal cells, such as adipocytes, fibroblasts, epithelial and endothelial cells and circulates in almost all human tissues as a zymogen that needs to be proteolytically activated to exert its biological functions.
View Article and Find Full Text PDFExtracellular vesicles (EVs) are nanosized heat-stable vesicles released by virtually all cells in the body, including tumor cells and tumor-infiltrating dendritic cells (DCs). By carrying molecules from originating cells, EVs work as cell-to-cell communicators in both homeostasis and cancer but may also represent valuable therapeutic and diagnostic tools. This review focuses on the role of tumor-derived EVs (TEVs) in the modulation of DC functions and on the therapeutic potential of both tumor- and DC-derived EVs in the context of immunotherapy and DC-based vaccine design.
View Article and Find Full Text PDFSponges (Porifera) are a diverse and globally distributed clade of benthic organisms, with an evolutionary history reaching at least the Ediacaran-Cambrian (541 Ma) boundary interval. Throughout their research history, sponges have been subjects of intense studies in many fields, including paleontology, evolutionary biology, and even bioengineering and pharmacology. The skeletons of sponges are mostly characterized by the presence of mineral elements termed spicules, which structurally support the sponge bodies, though they also minimize the metabolic cost of water exchange and deter predators.
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