Project description:Taxogenomic analyses of Starmerella gilliamiae f.a, sp. nov. and Starmerella monicapupoae f.a., sp. nov., two novel species isolated from flowers and insects
Project description:Adoptive transfer of regulatory T cells (Treg) is a promising new therapeutic option to treat detrimental inflammatory conditions. To reach sufficient cell yield for treatment, ex vivo isolated autologous or allogenic Tregs need to be expanded extensively in vitro during manufacturing of the Treg product. However, repetitive cycles of restimulation and prolonged culture have been shown to impact T cell phenotypes, functionality and fitness. We performed genome-wide DNA methylation profiling of cells throughout the manufacturing process of a polyclonal Treg product, which may be informative for predicting the cellular state and function of the final Treg product.
Project description:Genomic surveys of yeast hybrid species isolated from the wild and from human-related environment, aimed at the reconstruction of the natural evolution of Saccharomyces spp. evolution
Project description:Biotechnology-derived therapeutics manufacturing is highly regulated to assure product quality, safety and efficacy. Process conditions are closely monitored as they can influence product characteristics. Culture of mammalian cells at different scales is a vital part of biomanufacturing. Currently, scale up of bioreactors is largely done based on engineering parameters such as oxygen transfer and mixing characteristics. There is a lack of genomic translational studies in mammalian cell culture scale-up that can help delineate measurable cellular attributes for improved process understanding. These could be used for quantifying physiological response of cells due to changes in bioreactor environment. In this study, we identified 18 process-sensitive sentinel genes using microarray statistical analysis, which we further verified by qRT-PCR. These were differentially expressed transcripts between a typical 5 liter bench-scale bubble-aerated and impeller-agitated bioreactor and novel 35 mL high-throughput minibioreactors. Using expression changes and biochemical-pathway guidance of these sentinel genes, we were able to tune engineering parameters such that the improved scale-down resulted in both process parameter and sentinel gene profile convergence between the two systems, further solidifying the functionality evidence of these sentinel genes. This study serves as a starting point for developing qRT-PCR assays as comparability metrics that could be performed near-at-line during the cell culture process itself leading to enhanced process control. Additional broad applications of sentinel genes could be to validate different manufacturing facilities for the same product, and allow better process definition by fingerprinting the manufacturing process for more rapid biogenerics and vaccine approvals.
