Ani Arun and Shirley Galbiati 20.109 Proposal

Research Proposal Brainstorming

Scientific Questions and Engineering Goals

Inspired by the Hasty lab synchronized oscillator, we would like to construct a synchronized oscillator in mammalian cells. We would like to use this synchronized oscillator to form static spatial patterns of gene expression, as occurs naturally in the vertebrate segmentation process. Our project could shed light on the key processes that govern the vertebrate segmentation in development, as well as serve as a starting point for programmed patterned tissue formation and other applications in regenerative medicine.

In our implementation of the system, we would rely on fluorescent proteins as the readout of cell state. Experimental verification of our system would require time-lapse quantitative imaging techniques.

Background Information

This goal may require the use of a synthetic mammalian cell-cell communication mechanism. Thus far, none has been published. One idea is to use Delta and Notch signaling in cells that have the endogenous copies knocked out or knocked down. (More literature combing on this topic is needed). We would also need to come up with network topologies and a corresponding molecular implementation that could result in robust, synchronized oscillations. Finally, we hope that inspection of the current understanding of the role of FGF8 (fibroblast growth factor 8) in translating temporal segmentation clock pulses to spatial arrangement of segmentation boundaries will enable us to reach our pattern formation goal.