Metabolic engineering and synthetic biology in general are powerful areas of research, but they can only realize a quantum leap in breakthroughs when computational models involved in the Design-Build-Test-Learn engineering paradigm are standardized and implemented in the field. As part of our iGEM project, the models developed are motivated by different objectives and approaches in order to inform and be shaped by our endeavors in the lab. To do so, two different computational models were used to determine the best approaches to improve PHA yield and productivity in recombinant E. coli.

One of the ways to model a system in silico is through the dynamic model, which many systems biologists should be familiar with. By defining a pathway (such as the heterologous PHA biosynthetic pathway) or metabolic network as a series of ordinary differential equations (ODE), dynamic behaviors in the system over time may be predicted. A considerable limitation arises from the need for highly detailed information to parameterize the kinetics of the pathway; therefore, this type of model may be difficult to implement.

On the other hand, an organism as well-studied as E. coli enjoys a vast wealth of literature surrounding its genome and metabolic network. As a result, stoichiometric models such as genome-scale models (GEM) are available to be used for in silico simulations without necessitating the rigorous characterization associated with dynamic or kinetic models. Using this, we can investigate problems such as the best conditions to grow a recombinant SBM E. coli and how to improve the titer of PHA.

Dynamic modeling of the PHA biosynthetic pathway for PHBV co-polymer production

Overview 

Gold Medal Criterion #3

Convince the judges that your project's design and/or implementation is based on insight you have gained from modeling. This could be either a new model you develop or the implementation of a model from a previous team. You must thoroughly document your model's contribution to your project on your team's wiki, including assumptions, relevant data, model results, and a clear explanation of your model that anyone can understand.

The model should impact your project design in a meaningful way. Modeling may include, but is not limited to, deterministic, exploratory, molecular dynamic, and stochastic models. Teams may also explore the physical modeling of a single component within a system or utilize mathematical modeling for predicting function of a more complex device.

Please see the 2018 Medals Page for more information.