Cell behavior as cellular robotics: understanding and engineering living systems.

Within a volume of just a few picoliters, cells organize molecules and chemistry to build dynamic systems that move through, interact with and respond to their environment to perform complex behaviors like tiny robots. While the space of cell behaviors seen in nature is vast, much of this diversity arises from activating and organizing conserved molecular components in different ways through different patterns of spatiotemporal activity. The overarching theme of our group is to understand the patterns of activity that give rise to emergent dynamic cell behaviors, and use synthetic biology to engineer new patterns and behaviors that unlock the full potential of cells as technology.

current areas of focus:

Programmable reaction-diffusion systems for engineering synthetic spatiotemporal control of cell biology

A central tenet of cell biology is that the sub-cellular organization of signaling can control when and where downstream protein activities act. To define how different spatial patterns or dynamics influence the behavior of downstream cellular processes, we have developed a synthetic programmable reaction-diffusion platform for designing protein oscillations, patterns, and circuits in mammalian cells. Our strategy is based on repurposing bacterial positioning systems that are orthogonal to eukaryotes. By developing a plug-and-play platform that connects these patterns to host-cell proteins, we can synthetically pattern or probe cellular activities such as condensate assembly, actin filamentation, and cell signaling. Using this system, we aim to understand and engineer cell biology at length and timescales critical to biological function but previously inaccessible to synthetic control.

Synthetic protein circuits for encoding and decoding single-cell STATE INFORMATION in frequency-domain DATA STRUCTURES

Cell behaviors are driven by dynamic changes in the abundance, state, and localization of macromolecules. In single cells, these dynamics are typically tracked by measuring the intensity or localization of a fluorescence reporter over time, which can require precision instrumentation and suffers when changes are small and noisy. Electrical engineers overcome similar problems by coupling signals of interest to an easily measured high-frequency carrier signal, such as in AM and FM radio. Inspired by this, we have developed synthetic "cellular radio" circuits: genetically encoded protein oscillators that can act as tunable high-frequency carrier signals that act as frequency-domain probes for encoding and decoding dynamic cell-state data. When cells in a complex, mixed population possess different carrier frequencies, each cell acts like a different “radio station” that we can tune into and extract data from. We are currently exploring applications of cellular radios in dense fields of cells, organoids, and the tissues of living animals.

Mining EXOTIC protozoan SINGLE-CELL biology TO FIND generalizable design principles for organizing cell behavior

Metazoan cells represent only a small sliver of the design space of cellular forms and functions seen in nature. Single-cell protists, which often look and act like tiny animals, build extraordinary microscopic structures that detect and react to the environment on ultrafast timescales abound, but almost nothing is known about their molecular implementation or architecture. These remarkable cells have the potential to expand our understanding of how molecular components can be used to build microscopic machines. Our group is using predatory ciliates as model systems for understanding how structure and function are integrated across multiple timescales to perform tasks such as counting and hunting. By abstracting and generalizing the strategies we uncover, we aim to port the control logic of these systems to alternative cell types for synthtic biology applications.

Streaming video platforms for scientific exploration and outreach

The internet has eliminated barriers for communicating and sharing digitized scientific information, but is only beginning to increase access to the scientific process itself. The advent of streaming video technology platforms presents an opportunity to allow individuals all throughout the world to directly participate in science. To this end, we are developing a microscopy livestream project that will use ChatBots to allow users on Twitch.tv and Youtube Live to direct and control a microscope so as to explore pond-water microscopic aquariums derived from lake and pond samples throughout the great state of Wisconsin. Scientific users will be able to “clip” and annotate microscopy highlights that can be shared with an online community to directly participate in the scientific process while making important contributions to microscopic naturalism within the region.