The genetic bistable switch is a fundamental building block for engineering synthetic living systems. In synthetic biology, researchers have designed and constructed rudimentary bistable switches in E. coli and in mammalian cells. However, it remains challenging to construct a reusable, modular, switchable bistable switch in eukaryotes. In this project, I designed and built a novel switchable bistable switch in yeast, the model organism for eukaryotes. This switch can be switched on and off by adding two kinds of small molecules.
Biochemical oscillators are fundamental to understanding cell physiology, and present an ongoing challenge in building synthetic living systems. In synthetic biology, researchers have built a number of oscillators over the last decade resulting in various designs in organisms from E. coli to mammalian cells. However, especially in eukaryotic cells, a robust, tunable, and modular oscillator technology has yet to be demonstrated. In this project, I designed and analyzed a plant hormone induced oscillator in yeast. I developed mathematical model and showed that the oscillator could be achieved by tuning two key parameters. Currently I am working on experimental realizing this oscillator.
Aquarium is a smart laboratory operating system invented in the Klavins Lab where researchers can specify how to manipulate items that stored in the inventory using protocols and workflows written in computer codes. Adapted from the standard molecular cloning workflows, I wrote a majority of the codes in Ruby implementing two core molecular cloning workflows: plasmid construction and yeast cloning. These workflows take and batch users' inputs to the workflow and semi-automatically schedule the entire cloning process from ordering primers to Sanger sequencing verifications, resulting a nearly effortless cloning process in Aquarium. This technology also led to the startup Aquarium where I work as an engineer to build out the 21st century laboratory operating system, enabling reproducible and transferable workflows in biology labs and more.
I developed an experimental process in the Klavins Lab to interrogate frequency response for a synthetic auxin signaling pathway in yeast. The approach was using a microfluidic device called CellASIC to grow the yeast cell, where one can control the system precisely with different frequencies of auxin inputs and observe using fluorescence microscopy over time. I wrote Matlab based software to do image processing on the time course fluorescence images, which resulted in quantified time-course fluorescence data on the cells. Using the data, I generated a Bode plot describing the frequency response of signaling pathway. The result showed that this pathway works as a low-pass filter.