BMC Seminar Thursday 28 November, 12:00 in Læknagarður, Vatnsmýrarvegur 16, room 343
Title: Using Genome Scale Metabolic Models to Optimise Differentiation in Mesenchymal Stem Cells
Speaker: Dr. Sarah McGarrity, post-doctoral research fellow at the Systems Biology Laboratory, Faculty of Medicine, University of Iceland.
Abstract: Mesenchymal stem cells are a promising source of cells in regenerative medicine even though the early promise of using them has not yet been completely realised. Challenges that have contributed to the delay in realising this potential include production scaling issues, differentiation and difficulties maintaining the correct phenotype after re-implantation.
One area that may be optimised to improve cell growth and differentiation is metabolism. It is known that the metabolism of MSCs alters during differentiation. In particular how the availability of metabolites may affect the success of any implantation. Genome scale constraint based metabolic modelling is a framework to integrate and understand various data types; genomic, transcriptomic and metabolomics. It has long been used to optimise the growth and productivity of bacterial production systems and initial steps in applying this methodology to chondrocyte differentiation in MSCs have been made by another group. We are now using this methodology to apply to osteogenesis and adipogenesis.
We have combined transcriptomic data and new metabolic measurements in the CobraToolbox to create models of the early stages of expansion, adipogenic and osteogenic differentiation. By applying COBRA techniques to this data, such as the reporter metabolites and metabolic transition algorithms, we are able to explore the metabolic changes that favour osteogenesis or expansion.
The models were able to recreate known metabolic features of mesenchymal stem cells during expansion and differentiation. These include relative levels of oxidative phosphorylation and glycolysis, in the expansion versus the differentiation models, and production of kynurenine from tryptophan. By better understanding these metabolic changes during osteogenesis and their indirect effects it will be possible to optimise future growth and differentiation experiments.
Bio-sketch: Sarah McGarrity completed an undergraduate degree in genetics at the University of Cambridge and then Masters and PhD degrees in Systems Biology at the University of Newcastle, her PhD thesis was on Computational Modelling of Thiopurine Metabolism. After her PhD she began post-doctoral work at the University of Iceland working on endothelial cell metabolism with Óttar Rolfsson. Since 2017 she has worked with Óttar Rolfsson and Ólafur Sigurjónsson at the University of Reykjavík on the metabolism of mesenchymal stem cells. In February she will begin working on a joint project between the University of Iceland and Harvard Medical School on endothelial cell metabolism as a Novo Nordisk Foundation Post-doctoral research fellow.