Scramble and Synthetic Yeast

Synthetic biology offers us unprecedented control over genomes, their structure, and their arrangement. DNA can now be manipulated like never before. But what should we use this new capability to do?

In the 2019 Build-a-Genome course at BUGSS, we began to explore those questions. Using yeast cells with synthetic, man-made chromosomes, we used the designed Scramble system to rearrange (“Scramble”) those chromosomes to see what interesting properties we could evolve in the lab. We were able to generate yeast that were heat tolerant as well as able to survive in higher levels of caffeine and ethanol.

Yeast strains (one per column), showing that some have much stronger growth under high temperature conditions.
yeast Death
Yeast cells growing in the presence of an antifungal drug. Most cells have died, but a few survivors are much more resistant to the drug.

The Build-a-Genome course at BUGSS is part of the National Science Foundation-funded Build-a-Genome network. Participants from the course joined a national research network, and now 6 members are continuing this project to see how else we can use the Scramble system to learn more about genome structure, evolution, and gene regulation.

build a genome logo

For our ongoing research project, the BUGSS Scramble group is using the beautiful colors available through the Yeast Art project (below left; Yeast Art Project). These strains are normally used to produce amazing artworks (“Agar Art”;). We will be transferring these color pathways into strains with synthetic yeast chromosomes. By inducing the Scramble system, we will be able to produce a wide variety of color variation (below right; from In vitro DNA SCRaMbLE). By sequencing the genomes following Scramble, we’ll be able to see Taken together, this experiment will allow us to discover what what chromosomal alterations are responsible for the variation in pigment color, and this may help us to understand more about the biology of these genes.

The Yeast Art palette
The Yeast Art palette
Scrambling the beta-carotene pathway leads to dramatic variations in colors

Designing with living systems in the synthetic yeast project