Toolkit Provides Versatile Engineering Platform for Using Ancient Yeast Species in Today’s Labs
A team of investigators at the University of California (UC) Berkeley has developed a toolkit that helps researchers make greater use of a well-known species of yeast¾used by bakers and brewers since ancient times¾in cutting edge synthetic biology studies. In the past, these studies had most often worked with bacteria (single cells with a simple structure). The great advantage of yeast (also single-cell) is that it has cellular organization similar to that found in higher, multi-cellular organisms—including humans. This work was supported by the NSF-funded Synthetic Biology Engineering Research Center (Synberc), which is headquartered UC Berkeley.
Bacteria have long been the go-to for researchers since they are simple, easy to use, and thrive in diverse environments. Because yeast is fungus (not a plant, not an animal, but related to both) and a "higher" organism with an organized, protective nucleus that holds its chromosomes (like humans), experiments using yeast can yield information about how mammalian genes work and what happens when they don't work. The researchers focused on the yeast species saccharomyces cerevisiae because it was well-known and understood, but daunting to navigate and extract the tools needed for engineering applications. The toolkit developed by the research team addresses these problems and provides a versatile engineering platform for yeast—one that both simplifies the process by standardizing the physical manipulations and suggesting best practices. Specifically, yeast studies can clarify how genes are turned on or off, explain how cells that contain the same genes can be so different from one another, and help scientists sort out the orderly sequence of events in which a cell divides. As one example, this information can benefit millions of people, since many cancer drugs interfere with the same cell cycle.
Saccharomyces cerevisiae is growing in popularity as a chassis for synthetic biology due to its powerful genetic tools, extensively studied biology, and long history of industrial applications. The toolkit developed by the Synberc researchers simplifies and accelerates experimentation in this important model organism and enables more straightforward translation of materials and data from one group to another. The platform: (1) contains a rapid, modular assembly method and a basic set of characterized parts; (2) provides a framework in which to create new designs; and, (3) delivers essential data to inform those designs and genome-editing tools for making modifications directly to the yeast chromosomes. By relieving them of the burden of dealing with so many technical details, the toolkit allows researchers to focus on higher-level aspects of experimental design.
To develop the toolkit, the researchers adapted the MoClo (modular cloning) system, which categorizes cell parts as “types” based on their function and location in a completed device, and designates DNA characteristics of each type, allowing all parts of a particular type to be interchangeable. The major advantage of using a standardized system such as MoClo is that once parts are constructed, they are immediately available for incorporation into devices. This allows researchers to construct from parts a genetic structure in a cell carrying multiple gene expression devices in as little as two days—a powerful tool for approaching difficult problems in energy, agriculture, and human health.
