Improving Clostrodium toxoid vaccine production

My research is focused in the area of industrial biotechnology. Specifically, we use systems biology to identify bottlenecks in production of different organisms/cell lines used as cell factories. By using omics (transcriptomics, proteomics, metabolomics and fluxomics), we can measure thousands of biological variables throughout a controlled culture and identify markers of successful progression. We can find the active pathways and limiting substrates, and also compare between different conditions/cell lines. With this information, we improve the existing production systems, either by applying genetic engineering techniques or by culture medium/conditions optimisation. We have currently successfully applied this method to Chinese hamster ovary cells producing monoclonal antibodies and to the pathogen Clostridium tetani producing the tetanus toxin, which is then inactivated to use as a toxoid vaccine.

Biotechnology Engineer and M.Sc. in Chemical Engineering from the Universidad de Chile and PhD in Systems Biology and Industrial Biotechnology from The University of Queensland. Between 2009 and 2011 worked as analyst of technological businesses and project formulation in DICTUC SA and Pontificia Universidad Catolica de Chile (PUC).  Major awards include "Best Biotechnology Engineer, promotion 2009" given by the Institute of Engineers of Chile, and "Young Investigator Award" in the 2013 BioProcessing Network conference.

Key Publications

  1. Orellana C.A., Marcellin E., Gray P.P, Nielsen L.K. Overexpression of the regulatory subunit of glutamate-cysteine ligase enhances monoclonal antibody production in CHO cells. Biotechnology and Bioengineering, 2017, 114 (8): 1825-1836.
  2. de Oliveira Dal'Molin C.G., Orellana C., Gebbie L., Steen J., Hodson M.P., Chrysanthopoulos P., Plan M.R., McQualter R., Palfreyman R.W., Nielsen L.K. Metabolic Reconstruction of Setaria italica: A Systems Biology Approach for Integrating Tissue-Specific Omics and Pathway Analysis of Bioenergy Grasses. Frontiers in Plant Science, 2016, 7: 1138.
  3. Hefzi, H., Ang, K.S., Hanscho, M., Bordbar, A., Ruckerbauer, D., Lakshmanan, M., Orellana, C.A., Baycin-Hizal, D., Huang, H., Ley, D., Martínez, V.S., Kyriakopoulos, S., Jiménez, N.E., Zielinski, D.C., Quek, L.E., Wulff, T., Arnsdorf, J., Li, S., Lee, J.S., Paglia, G., Loira, N., Spahn, P.N., Pedersen, L.E., Gutierrez, J.M., Lund, A.M., Nagarajan, H., Thomas, A., Abdel-Haleem, A.M., Zanghellini, J., Kildegaard, H.F., Voldborg, B.G., Gerdtzen, Z.P., Betenbaugh, M.J., Palsson, B.O., Andersen, M.R., Nielsen, L.K., Borth, N., Lee, D.Y., Lewis, N.E. A consensus genome-scale reconstruction of CHO cell metabolism for improved biotherapeutic protein production. Cell Systems, 2016, 3 (5): 434–443.e8.
  4. Swainston, N., Smallbone, K., Hefzi, H., Dobson, P.D., Brewer, J., Hanscho, M., Zielinski, D.C., Ang, K.S., Gardiner, N.J., Gutierrez, J.M., Kyriakopoulos, S., Lakshmanan, M., Li, S., Liu, J.K., Martínez, V.S., Orellana, C.A., Quek, L.E., Thomas, A., Zanghellini, J., Borth, N., Lee, D.Y., Nielsen, L.K., Kell, D.B., Lewis, N.E., Mendes, P. Recon 2.2: from reconstruction to model of human metabolism. Metabolomics, 2016, 12: 1-7.
  5. Orellana C. A., Marcellin E., Schulz B.L., Nouwens A.S., Gray P.P, Nielsen L.K. High antibody- producing Chinese hamster ovary cells up-regulate intracellular protein transport and glutathione synthesis. Journal of Proteome Research, 2015, 14 (2): 609–618.
  6. Orellana C.A., Shene C. , Asenjo J.A. Mathematical Modeling of Elution Curves for a Protein Mixture in Ion Exchange Chromatography Applied to High Protein Concentration. Biotechnology and Bioengineering, 2009, 104 (3): 572-581