Alladi Ramakrishnan Hall

And the rest is Math: Systems Biology Approaches to investigate temozolomide resistance in Glioblastoma

Anuradha Raghunathan

Chemical Engineering Division CSIR-National Chemical Laboratory (NCL), Pune

Intrinsic to systems biology (the holistic study of interacting genes and gene products of an organism) is the notion that biological systems have “emergent properties”. Such biological outcomes cannot be predicted by traditional reductionist for prokaryotes, let alone eukaryotes. Any organism can be represented qualitatively as a genome-scale biochemical reaction network reconstruction. Such reconstructions are essentially stoichiometric representations of reactions that define cellular function and can be converted into a mathematical format to compute cell phenotype. Further, use of a constraints-based modeling philosophy allows simulating the physiological function of the cell's complex networks and interactions. The ability to compute and predict cell function allows us diverse applications ranging from designing and engineering cells for biotechnology to understanding pathogenesis in medicine. In this talk, I will discuss the paradigm of metabolic systems biology. I will give an overview of the work done in our laboratory to build such models for brain cancer or glioblastoma I will highlight the use of such models to understand the emergent phenomenon of drug
resistance from a metabolic standpoint. The talk will discuss these results in the context of a constraints-based tissue specific flux balance model of human metabolism. Such models not only explain the heterogeneity of cells and predict differences in the drug response but can predict alternate targetable cell vulnerabilities. Such scalable work flows could fill a critical need for predictive models for tumor growth and proliferation in personalized medicine.