Engineering Fellowships For Growth: Designing Feedback Control in Biology for Robustness and Scalability

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Synthetic Biology is the "Engineering of Biology": it aspires to use the Engineering design cycle to produce bio-circuits that behave predictably and reliably, usually with specific applications in mind. Synthetic Biology has the potential to create new industries and technologies in several sectors, from agriculture to the environment, and from energy to healthcare. Some of these applications require Synthetic Biology designs to be scalable, so that small circuits can be composed to form larger systems. Currently, however, even small bio-circuits seldom function as expected because of the high level of uncertainty in the cellular environment, the way poorly-characterized parts are assembled together and the lack of a systematic framework for integrating parts to form systems. This is a major challenge that needs to be overcome in order for the potential of Synthetic Biology to be fulfilled and for industry and society to reap the rewards.Natural systems use several mechanisms to overcome this major challenge. The most important one involves careful use of feedback control. This is done at all levels of organization - from the genetic, metabolic, cellular to the systems level. The regulation of biochemical processes inside a cell is key for ensuring robust functionality despite the high levels of environmental uncertainty and intrinsic and extrinsic noise.This Fellowship application will use a systems and control engineering approach, based on modelling, abstraction, standardization and the development of new bio-feedback modules to target specific uncertainties in the cell. I will create an interdisciplinary research team which will demonstrate that through careful design and implementation of feedback control components, the functionality of the rest of the designed circuitry can be made robust and allow scalability. The feedback designs will be done at multiple organizational scales and interactions (genetic, signalling and cell-cell), which will be implemented in the laboratory, demonstrating the effectiveness of the approach.