College of Science & Engineering
Genomic data from high-throughput sequencing are used to assemble de novo the whole genome of Chinese hamster and CHO cells. These cells are important because of their extensive use for the production of recombinant protein therapeutics by the biopharmaceutical industry. The genomic resources for these cells are rather sparse, therefore building genomic information is incredibly useful towards improving bioprocessing. These researchers have studied the transcriptome of these cells to determine diversity of gene expression among different CHO host cells. The quality of the product produced potentially depends on the expression pattern of certain genes in the host cells. The depth of sequencing was also used to identify mutations in CHO cells that potentially enable them to grow in continuously in culture. The researchers used genomic information to verify these mutations. They also used the genomic reads to indentify copy number variants in high-producing CHO cells. Along with these studies, other insights from analysis of Chip-Seq and Bisulfite sequencing of CHO cells are useful in the advancement of bioprocessing of recombinant protein therapeutics. The researchers have also done ATAC-Seq analysis on CHO cells to identify open regions of chromatin as well as RNA-seq to look at the transcriptional activity of various cell lines. Recently, the researchers have also begun looking for structural variants as the sequence level in different CHO cell lines. The kinetic model is further used as the deterministic model for the group's newly developed optimization algorithm to guide new designs of the new engineered CHO cells. All of this data can be integrated with transcriptome and CGH to identify stable regions ideal for transgene integration.
The group's newest research areas involve understanding the transcriptional profiles of human cells during virus (both AAV and influenza) infection using RNA-seq and understanding changes in Natural Killer cell transcriptional profiles over the course of activation and expansion, steps which are necessary if these cells are to be used as a therapy in the future.