Chapter 12: Cell culture metabolomics and lipidomics
by Irina Alecu, Carmen Daniela Sosa-Miranda, Jagdeep K. Sandhu, Steffany A.L. Bennett, Miroslava Cuperlovic-Culf
Abstract
Cell cultures are one of the most useful tools in life sciences research and biotechnology, irreplaceable for applications as diverse as testing of drugs or toxins, development of gene and cell therapies, investigation of function of biomolecules, production of biologics or vaccine particles. Metabolomics and lipidomics with their closest link to cell phenotype and as indicators of functional effects and changes in biological systems provide a highly valuable window into many applications of cell cultures. These omics tools can be used for real time monitoring of cell culture growth and state, provide detailed, non-biased analysis of changes within cells or in secreted media or extracellular vesicles. Metabolomics can be used to optimize cell growth for enhanced production in bioreactor applications or for monitoring cell health, for example in cell therapy development. In this chapter we will outline some examples and methods used in metabolomics and lipidomics of cell cultures including analysis of cells, media and extracellular vesicles. Experimental method presentation is followed by introduction to analysis and modeling tools including statistical, mechanistic and machine learning methods with particular relevance in the applications of metabolomics and lipidomics in cell cultures.
Irina Alecu

Dr. Irina Alecu is a lipid biochemist whose research focuses on using and developing novel liquid chromatography mass spectrometry methods to understand the mechanistic role played by lipids in neurodegenerative diseases. She is the Team Lead of the Discovery Research and Target Research programs of the India Taylor Lipidomics Platform and Neural Regeneration Laboratory at the University of Ottawa. Dr. Alecu has discovered previously unidentified lipids and elucidated a novel metabolic pathway of 1-deoxysphingolipids, toxic lipids which were thought to be dead-end metabolites. Together with Dr. Steffany Bennett, she is currently working on developing diagnostic and prognostic mass spectrometry panels wherein the lipidome can be used to predict susceptibility and resistance to devastating neurodegenerative diseases.
Steffany A.L. Bennett

Dr. Steffany Bennett is a lipid biochemist and systems neurobiologist working to identify gender and sex-specific differences in lipid metabolism associated with neurodegenerative disease. She a Full Professor and University Research Chair in Neurolipidomics at the University of Ottawa. She is also the Director of the India Taylor Lipidomics Research Platform, Associate Director of the Centre for Catalysis Research and Innovation, Co-Director of the NSERC CREATE Matrix Metabolomics Training Program, and Special Advisor to the President on Equity, Diversity, and Inclusion. Her area of expertise is in the use of high-performance liquid chromatography electrospray ionization tandem mass spectrometry as applied to neurolipidomics and to evidence-based personalized precision medicine focusing on how lipid metabolism dictates vulnerability and resilience to genetic determinants of neurodegenerative disease. To achieve this goal, her research incorporates not only a GBA+ approach but also seeks to embed principles of equity diversity and inclusion into all aspects of metabolic research.
Miroslava Cuperlovic-Culf

Miroslava Cuperlovic-Culf (Ph.D. UCSB, USA; PDF, UBC, Canada), is a Senior Research Officer and Team Leader in Digital Technologies Research Centre of National Research Council of Canada and Adjunct Professor at Department of Biochemistry, Microbiology, and Immunology, University of Ottawa. Her work is in computational biology and bioinformatics where she is using data mining, AI and mathematical modeling to gain knowledge from high throughput molecular data with particular interest in metabolomics and lipidomics. Of note are her contributions combining metabolomics with cell modeling and network analysis and applied to diagnostic and treatment discovery.