A complete insight into the biological behaviour of a complex system entails pursuing a comprehensive approach, which consists of monitoring global changes at the genome, transcriptome, proteome and metabolome levels. The "-omics" platform includes technical capabilities for acquiring data at these multiple levels, which are subsequently utilised in various applications to improve our understanding of microbial and mammalian cellular systems.
The Proteomics laboratory hosts a repertoire of instrumentation for protein identification, quantitative protein expression profiling and mapping of post translational modifications. 2D Gel electrophoresis is used to separate protein mixtures. Replicate gel maps are compared and differentiating proteins are isolated, digested and identified by mass spectrometry (MS). Metabolic labelling of proteins with stable isotopes and peptide isobaric tagging is used to quantitatively compare the expression levels of proteins by MS. Tandem MS is performed to obtain peptide sequence information to identify proteins and to quantify labelled peptides.
Metabolomics refers to the global study of small organic molecules with a molecular weight of less than 1000 Da. At BTI, metabolomics is used to study metabolic behaviour related to cell growth, apoptosis and protein productivity. Initial exploration of the metabolome is carried out using ultra performance liquid chromatography-mass spectrometry (UPLC-MS).
The resulting raw MS data is pre-processed and analysed with MetaSuite, an in-house developed software. Targeted profiling of shortlisted metabolites of interest is subsequently carried out via the multiple reaction monitoring (MRM) approach. The resulting information contributes towards improvements in cell culture processes, through guiding the development of optimal culture media and the identification of new targets for cell line engineering.
The Microarray Group studies the genetic circuitry underlying cellular metabolism, growth death and protein glycosylation during high cell density production processes and protein-free media adaptation. The research programmes in BTI revolve around identifying targets for genetic engineering of production cell lines leading to enhanced cell viability and productivity.
The Systems Biology Group's research is focused on the development of integrative and systemic approaches to characterize and engineer mammalian and microbial systems for enhanced bioprocessing. The group has developed various software platforms, including programs for analysis of genomic and transcriptomic Next Generation Sequencing experiments, LC-MS data pre-processing, as well as glycan profile visualization.
The Systems Biology Group also has rich experience in developing predictive computational models of biological processes from global cellular information such as omics-data to find proteins, genes and metabolites which are highly correlated with various physiological states such as cell growth, apoptosis and antibody production. This integrated framework allows the group to pursue rational approach for identifying engineering targets in cell line engineering and optimization of media/feed components to improve cell density, growth, product yields and/or reduce secretion of undesirable by-products.