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Enabling Technologies for Multi-scale Modeling

Organisms have a remarkable ability to process changes and adapt to their environment. A clear understanding of how pathways operate with respect to each other and in the combined contexts of the intracellular state and external environment is necessary to formulate accurate predictions regarding cell fate. The tremendous impact of such predictive power is the guidance it provides for creating designer circuits that will enable early detection, diagnosis and ultimately cures for genetic disorders.

 

Facilitating technologies to reengineer biological circuits will require systems level optimization that comes from a deep understanding of operational relationships among all of a cell’s constituent parts. Deconstruction of transcriptional networks into accurate, statistically predictive models requires tight control over culture parameters and perturbations. To achieve this, we are developing a multiplexing bioreactor that allows controlled perturbation of 16 independent culture chambers.

 

Automated decisions regarding perturbations and the state of the culture are made based on user defined protocol and sensor measurements (OD, temperature, pH, etc.). The system can be configured to run in batch, chemostatic, and/or serial dilution modes. Furthermore, the instrument will be integrated with our existing micro-fluidic platform to establish a complete multi-scale culture, manipulation and measurement system.

 

The unique advantage of this device is that it will provide a global perspective on cellular responses over large populations, as well as a detailed measurement of single-cell responses. The coupling of these two otherwise diametrically opposed approaches will provide avenues for the type of multi-scale modeling necessary for systems reengineering.