Chemical Engineering Seminar
Metabolism is the core of functioning of any cell as it ensures provision of Gibbs free energy as well as precursors for synthesis of cellular constituents like proteins, lipids and DNA. Metabolism involves a large number of biochemical conversion processes. Thus, even Baker's yeast, that serves as the most simple model for studying human cells, contains more than 900 enzymes that catalyze more than 2,500 biochemical reactions. In human cells these numbers are much larger with more than 3,000 enzymes and more than 5,000 biochemical reactions. Even though the large number of reactions are organized into metabolic pathways, there is a high degree of connectivity between the reactions, and hence it is complicated to study these reactions individually. It is therefore necessary to take a systemic approach for analysis of metabolism, often referred to as systems biology. We have generated so-called genome-scale metabolic models (GEMs), that are comprehensive description of cellular metabolism, for a number of different organisms, including yeast, human cells and gut symbionts. Recently we have advanced these models to incorporate kinetic information as well as proteome constraints, which has significantly improved the predictive strength of these models. In this talk I will demonstrate the concept of these models by describing in details a model for yeast, and show how this model can be used in combination with multi-omics analysis to get new insight into global regulatory structures in metabolism. I will then demonstrate how this modeling concept can be taken to study human metabolism, in particular to get insight into metabolic reprogramming associated with neoplastic transformations. Finally, I will discuss how this modeling concept also can be used to get insight into the gut microbiome, which is a complex ecosystem that interacts closely with human metabolism and therefore impacts our health status.