Biopharma Research at the NICB
Animal cells, especially the Chinese hamster ovary cell line (CHO), are the most important production vehicle for making recombinant human proteins, such as cytokines and antibodies, for human therapeutic use. This field represents an important opportunity for future development of the pharmaceutical industry and a significant area for employment of scientists in Ireland. Understanding of the basic biology underpinning the CHO production system is lacking - the field has developed on a pragmatic basis without a high level of understanding of the cellular molecular biology involved.
In collaboration with a number of leading international biopharmaceutical companies and academic collaborators NICB scientists are applying state-of-the-art technologies in expression microarrays, bioinformatics and proteomics to profile gene and protein expression patterns associated with desirable production phenotypes. We are also investigating the role of candidate pathways using functional genomics approaches such as siRNA and cDNA transfection. Lab facilities for cell fermentation in NICB allow testing new hypotheses on a small to medium scale before they are passed on to our industrial collaborators for larger-scale validation.
Click here to meet the CHO research group
Kelly PS, Gallagher C, Clynes M, Barron N. (2015) Conserved microRNA function as a basis for Chinese hamster ovary cell engineering. Biotechnol Lett. 2015 Apr;37(4):787-98. doi: 10.1007/s10529-014-1751-7. Epub 2014 Dec 21.
- Sanchez N, Kelly P, Gallagher C, Lao NT, Clarke C, Clynes M, Barron N. (2013) CHO cell culture longevity and recombinant protein yield are enhanced by depletion of miR-7 activity via sponge decoy vectors. Biotechnol J. 9: 396-404.
- Sanchez N, Gallagher M, Lao N, Gallagher C, Clarke C, Doolan P, Aherne S, Blanco A, Meleady P, Clynes M, Barron N. (2013) MiR-7 triggers cell cycle arrest at the G1/S transition by targeting multiple genes including Skp2 and Psme3. PLoS One 8, e65671 PMID 23762407.
- Doolan P, Barron N, Kinsella P, Clarke C, Meleady P, O'Sullivan F, Melville M, Leonard M, Clynes M (2012) Microarray expression profiling identifies genes associated with regulating sustained cell specific productivity (S-Qp) in CHO K1 production cell lines. Biotechnol J. 7, 516-526.
- Barron N, Sanchez N, Kelly P, Clynes M (2011) MicroRNAs: tiny targets for engineering CHO cell phenotypes? Biotechnol Lett. 33, 11-20.
- Barron N, Kumar N, Sanchez N, Doolan P, Clarke C, Meleady P, O’Sullivan F, Clynes M (2011). Engineering CHO cell growth and recombinant protein productivity by overexpression of mir-7. J. Biotech. 151, 204-211.
- Clarke C, Doolan P, Barron N, Meleady P, Madden SF, Dinino D, Leonard M, Clynes M. (2011). CGCDB: A web-based resource for the investigation of gene coexpression in CHO cell culture. Biotechnol Bioeng., 109: 1368-1370.
- Clarke C, Doolan P, Barron N, Meleady P, O'Sullivan F, Gammell P, Melville M, Leonard M, Clynes M. (2011) Large scale microarray profiling and co-expression network analysis of CHO cells identifies transcriptional modules associated with growth and productivity. J Biotechnol. 155(3):350-9.
- Clarke C, Doolan P, Barron N, Meleady P, O’Sullivan F, Gammell P, Melville M, Leonard M, Clynes M (2011) Predicting cell-specific productivity from CHO gene expression. J. Biotech., 151: 159-165.
- Melville M, Doolan P, Mounts W, Barron N, Hann L, Leonard M, Clynes M, Charlebois T. (2011) Development and characterisation of a Chinese Hamster Ovary (CHO) cell-specific oligonucleotide microarray. Biotechnol. Letts 33, 1773-9.
- Doolan P, Meleady P, Barron N, Henry M, Gallagher R, Gammell P, Melville M, Sinacore M, McCarthy K, Leonard M, Charlebois T, Clynes M (2010) Microarray and proteomics expression profiling identifies several candidates, including the valosin-containing protein (VCP), involved in regulating high cellular growth rate in production CHO cell lines. Biotechnol Bioeng. 106(1):42-56