Abstract
Recent studies have demonstrated the utility of DNA microarray technology in engineering cellular properties. For instance, cellular adhesion, the necessity of cells to attach to a surface in order to to proliferate, was examined by comparing two distinct HeLa cell lines. Two genes, one encoding a type II membrane glycosylating sialyltransferase (siat7e) and the other encoding a secreted glycoprotein (lama4), were found to influence adhesion. The expression of siat7e correlated with reduced adhesion, whereas expression of lama4 correlated with increased adhesion, as shown by various assays. In a separate example, a gene encoding a mitochondrial assembly protein (cox15) and a gene encoding a kinase (cdkl3), were found to influence cellular growth. Enhanced expression of either gene resulted in slightly higher specific growth rates and higher maximum cell densities for HeLa, HEK-293, and CHO cell lines. Another investigated property was the adaptation of HEK-293 cells to serum-free media. The genes egr1 and gas6, both with anti-apoptotic properties, were identified as potentially improving adaptability by impacting viability at low serum levels. In trying to control apoptosis, researchers found that by altering the expression levels of four genes faim, fadd, alg-2, and requiem, apoptotic response could be altered. In the present work, these and related studies in microorganisms (prokaryote and eukaryote) are examined in greater detail focusing on the approach of using DNA microarrays to direct cellular behavior by targeting select genes.
Similar content being viewed by others
References
Jaluria, P., Konstantopoulos, K., Betenbaugh, M., & Shiloach, J. (2007). A perspective on microarrays: Current applications, pitfalls, and potential uses. Microbial Cell Factories, 6, 4.
Gill, R. T. (2003). Enabling inverse metabolic engineering through genomics. Current Opinion in Biotechnology, 14, 484–490.
Schena, M., Shalon, D., Davis, R. W., & Brown, P. O. (1995). Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science, 270, 467–470.
Griffin, T. J., Seth, G., Xie, H., Bandhakavi, S., & Hu, W. S. (2007). Advancing mammalian cell culture engineering using genome-scale technologies. Trends in Biotechnology, 25, 401–408.
Chang, T. M., & Prakash, S. (2001). Procedures for microencapsulation of enzymes, cells and genetically engineered microorganisms. Molecular Biotechnology, 17, 249–260.
Jaluria, P., Betenbaugh, M., Konstantopoulos, K., Frank, B., & Shiloach, J. (2007). Application of microarrays to identify and characterize genes involved in attachment dependence in HeLa cells. Metabolic Engineering, 9, 241–251.
Majors, B. S., Betenbaugh, M. J., & Chiang, G. G. (2007). Links between metabolism and apoptosis in mammalian cells: Applications for anti-apoptosis engineering. Metabolic Engineering, 9, 317–326.
Khoo, S. H., & Al-Rubeai, M. (2007). Metabolomics as a complementary tool in cell culture. Biotechnology and Applied Biochemistry, 47, 71–84.
Korke, R., Rink, A., Seow, T. K., Chung, M. C., Beattie, C. W., & Hu, W. S. (2002). Genomic and proteomic perspectives in cell culture engineering. Journal of Biotechnology, 94, 73–92.
Lum, A. M., Huang, J., Hutchinson, C. R., & Kao, C. M. (2004). Reverse engineering of industrial pharmaceutical-producing actinomycete strains using DNA microarrays. Metabolic Engineering, 6, 186–196.
Jaluria, P. (2007). The use of microarrays and related genomics tools to reverse engineer mammalian cell culture targeting specific cellular features with application in biotechnology, Ph.D. thesis, Johns Hopkins University, Baltimore, MD.
Quackenbush, J. (2001). Computational analysis of microarray data. Nature Reviews. Genetics, 2, 418–427.
Hatzimanikatis, V., Lee, K. H., & Bailey, J. E. (1999). A mathematical description of regulation of the G1-S transition of the mammalian cell cycle. Biotechnology and Bioengineering, 65, 631–637.
Bailey, J. E., Sburlati, A., Hatzimanikatis, V., Lee, K., Renner, W. A., & Tsai, P. S. (2002) Inverse metabolic engineering: A strategy for directed genetic engineering of useful phenotypes. Biotechnology and Bioengineering, 79, 568–579.
Pollard, T. D. & Earnshaw, W C. (2004). Cell biology. Philadelphia, PA: Saunders.
Jaluria, P., Betenbaugh, M., Konstantopoulos, K., & Shiloach, J. (2007). Enhancement of cell proliferation in mammalian cells by gene insertion of a cyclin-dependent kinase homolog. BMC Biotechnology, 7, 71.
Even, M. S., Sandusky, C. B., & Barnard, N. D. (2006). Serum-free hybridoma culture: Ethical, scientific and safety considerations. Trends in Biotechnology, 24, 105–108.
Sinacore, M. S., Drapeau, D., & Adamson, S.R. (2000). Adaptation of mammalian cells to growth in serum-free media. Molecular Biotechnology, 15, 249–257.
van der Valk, J., Mellor, D., Brands, R., Fischer, R., Gruber, F., Gstraunthaler, G., Hellebrekers, L., Hyllner, J., Jonker, F. H., Prieto, P., Thalen, M., & Baumans, V. (2004). The humane collection of fetal bovine serum and possibilities for serum-free cell and tissue culture. Toxicology In Vitro, 18, 1–12.
Jaluria, P., Konstantopoulos, K., Betenbaugh, M. & Shiloach, J. (2008). Egr1 and gas6 facilitate the adaptation of HEK-293 cells to serum-free media by conferring enhanced viability and higher growth rates. Biotechnology and Bioengineering, 99(6), 1443–1452.
Goswami, J., Sinskey, A. J., Steller, H., Stephanopoulos, G. N., & Wang, D. I. (1999). Apoptosis in batch cultures of Chinese hamster ovary cells. Biotechnology and Bioengineering, 62, 632–640.
Arden, N., Majors, B. S., Ahn, S. H., Oyler, G., Betenbaugh, M. J. (2007). Inhibiting the apoptosis pathway using MDM2 in mammalian cell cultures. Biotechnology and Bioengineering, 97, 601–614.
Wong, D. C., Wong, K. T., Lee, Y. Y., Morin, P. N., Heng, C. K., & Yap, M. G. (2006). Transcriptional profiling of apoptotic pathways in batch and fed-batch CHO cell cultures. Biotechnology and Bioengineering, 94, 373–82.
Sahm, H., Eggeling, L., Eikmanns, B., & Kramer, R. (1995). Metabolic design in amino-acid producing bacterium Corynebacterium glutamicum. FEMS Microbiology Reviews, 16, 243–252.
Sindelar, G., & Wendisch, V. F. (2007). Improving lysine production by Corynebacterium glutamicum through DNA microarray-based identification of novel target genes. Applied Microbiology and Biotechnology, 76, 677–689.
Imaizumi, A., Takikawa, R., Koseki, C., Usuda, Y., Yasueda, H., Kojima, H., Matsui, K., & Sugimoto, S. (2005). Improved production of l-lysine by disruption of stationary phase-specific rmf gene in Escherichia coli. Journal of Biotechnology, 117, 111–118.
Gill, R. T., DeLisa, M. P., Valdes, J. J., & Bentley, W. E. (2001). Genomic analysis of high-cell-density recombinant Escherichia coli fermentation and “cell conditioning” for improved recombinant protein yield. Biotechnology and Bioengineering, 72, 85–95.
Oh, M.K., & Liao, J.C. (2000). Gene expression profiling by DNA microarrays and metabolic fluxes in Escherichia coli. Biotechnology Progress, 16, 278–286.
Boccazzi, P., Zanzotto, A., Szita, N., Bhattacharya, S., Jensen, K.F., & Sinskey, A.J. (2005). Gene expression analysis of Escherichia coli grown in miniaturized bioreactor platforms for high-throughput analysis of growth and genomic data. Applied Microbiology and Biotechnology, 68, 518–532.
Hirasawa, T., Yoshikawa, K., Nakakura, Y., Nagahisa, K., Furusawa, C., Katakura, Y., Shimizu, H., & Shioya, S. (2007). Identification of target genes conferring ethanol stress tolerance to Saccharomyces cerevisiae based on DNA microarray, Data Analysis, 131, 34–44.
Acknowledgments
Funding was provided by the intramural program at the National Institute of Diabetes & Digestive & Kidney diseases, National Institute of Health.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jaluria, P., Chu, C., Betenbaugh, M. et al. Cells by Design: A Mini-Review of Targeting Cell Engineering Using DNA Microarrays. Mol Biotechnol 39, 105–111 (2008). https://doi.org/10.1007/s12033-008-9048-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12033-008-9048-5