CHO-Omics Review: The Impact of Current and Emerging Technologies on Chinese Hamster Ovary Based Bioproduction.

CHO cells are the most prevalent platform for modern bio-therapeutic production. Currently, there are several CHO cell lines used in bioproduction with distinct characteristics and unique genotypes and phenotypes. These differences limit advances in productivity and quality that can be achieved by the most common approaches to bioprocess optimization and cell line engineering. Incorporating omics-based approaches into current bioproduction processes will complement traditional methodologies to maximize gains from CHO engineering and bioprocess improvements. In order to highlight the utility of omics technologies in CHO bioproduction, the authors discuss current applications as well as limitations of genomics, transcriptomics, proteomics, metabolomics, lipidomics, fluxomics, glycomics, and multi-omics approaches and the potential they hold for the future of bioproduction. Multiple omics approaches are currently being used to improve CHO bioprocesses; however, the application of these technologies is still limited. As more CHO-omic datasets become available and integrated into systems models, the authors expect significant gains in product yield and quality. While individual omics technologies provide incremental improvements in bioproduction, the authors will likely see the most significant gains by applying multi-omics and systems biology approaches to individual CHO cell lines.

Three distinct isoforms of ATP synthase subunit c are expressed in T. brucei and assembled into the mitochondrial ATP synthase complex.

One striking feature of the biology of trypanosomes is the changes in mitochondrial structure and function that occur as these parasites transition from one life cycle stage to another. Our laboratory has been interested in the role the mitochondrial ATP synthase plays in mitochondrial changes through the life cycle. Analysis of the recently completed T. brucei genome suggested that there may be multiple putative genes encoding ATP synthase subunit c. While homologous in their 3' ends, these genes differ in their 5' ends and, if expressed, would result in three distinct proteins. Our analysis showed that all three of the possible transcripts were detected in both procyclic and bloodstream stages, although the c-3 transcript was less abundant than that for c-1 or c-2. The three isoforms of subunit c are produced in both the bloodstream and procyclic stages and their mature protein products possess distinct N-terminal regions of the protein as found within mitochondria. All three isoforms are also incorporated into the assembled ATP synthase complex from procyclic cells. Although multiple subunit c genes have been found in other organisms, they produce identical polypeptides and the finding of significant differences in the mature proteins is unique to T. brucei.