Model-driven approach to engineering mammalian cells for the production of glycosylated protein
Protein N-glycosylation is often a critical quality attribute in the production of therapeutic proteins. Chris Stach, Meghan McCann, and Conor O'Brien, et al. describe a model-driven approach to engineering mammalian cells for the production of glycosylated proteins. Utilizing a rapid synthetic biology gene assembly pipeline, this work was made possible through collaboration between Mike Smanski (Biochemistry, UMN) and the Hu lab.
ACS Synth. Biol., DOI 10.1021/acssynbio.9b00215
Rewiring the Warburg effect: metabolic engineering design through kinetic model optimization
In a collaboration between Prodromos Daoutidis and the Hu lab, Conor O’Brien et al. developed a framework using optimization of a mechanistic kinetic model of metabolism to determine combinations of genes that can be used to alter cell metabolism. This framework was then applied rewire the Warburg effect, identifying small combinations of gene changes that could lead to dramatic reductions in the rate of lactate production during cell growth.
(Metabolic engineering, 2019, Vol.56, DOI: 10.1016/j.ymben.2019.08.005)
A tool for visualization of O-glycosylation networks
A visualization tool was developed for O-glycosylation networks using a rule-based network generator by Tung Le, Conor O’Brien, Udit Gupta, et al. in collaboration with Prodromos Daoutidis and the Hu lab. This tool allows rapid testing of the effects of gene additions or knockouts on the overall glycan network produced by a given cell, detection of specific glycan epitopes, and visualization of experimental data.
(Biotechnology and bioengineering, 2019, Vol.116(6), DOI: 10.1002/bit.26952)
Transcriptionally active regions for transgene integration
Sofie O’Brien et al. combined information on transcriptional activity from RNAseq data and chromatin accessibility from ATAC sequencing to identify desirable sites for transgene integration. This approach streamlines the development of new product producing cell lines.
(Biotechnol. J. 13: 1800226. DOI 10.1002/biot.201800226)
Stochasticity in the transfer of antibiotic resistance plasmids
A collaboration between Gary Dunny (Microbiology UMN) and the Hu lab combined modeling and HCR FISH to demonstrate stochasticity in the transfer of antibiotic resistance plasmids in Enterrococcus faecalis, where transfer can occur despite unfavorable pheromone conditions.
(Breuer, Bandyopadhyay, et al. PLoS Genet., 13:e1006878, DOI 10.1371/journal. pgen.1006878)
Meta-analysis of transcriptomes for hepatocyte cell differentiation
Ravali Raju et al. described a meta-analysis approach that enabled gene expression data of in vitrodifferentiation of hepatocyte-like cells from stem cells and mouse embryonic liver development to be integrated for analysis. Through aligning the metadata chronologically they concluded that the current HLC derived from pluripotent stem cells all reached an immature stage that is equivalent to mouse embryo liver at ~E14.
(Stem Cells and Development, 27:910-921, DOI 10.1089/scd.2017.0270)