Scientists Create 'Designer Yeast' in Significant Step toward Synthetic Life

By Kaplan, Sarah | The Charleston Gazette (Charleston, WV), March 10, 2017 | Go to article overview

Scientists Create 'Designer Yeast' in Significant Step toward Synthetic Life


Kaplan, Sarah, The Charleston Gazette (Charleston, WV)


In a significant advance toward creating the first "designer complex cell, scientists say they are one-third of the way to synthesizing the complete genome of baker's yeast. In seven studies published Thursday in the journal Science, the researchers describe how they built six of the 16 chromosomes required for the yeast Saccharomyces cerevisiae, altering the genetic material to edit out some genes and write in new characteristics.

"A lot of synthetic biology is motivated by this idea that ... you only understand something when you can build it, said Johns Hopkins computational biologist Joel Bader, one of the leaders of the project. "Well, now we know enough about biological systems that we can design a chromosome on a computer, synthesize it in a laboratory, put it in the cell, and it will work.

Scientists have built designer cells in the past. In 2010, scientists at the J. Craig Venter Institute created a bacterial cell controlled by a synthesized genome by copying the DNA of one bacterium into another. Last year they took the effort a step further by building the first "minimal cell, an organism never found in nature that had the smallest number of genes required for life. Several months later, a team led by researchers at Harvard Medical School successfully re-engineered a small fraction of the genes of the bacterium E. coli.

This isn't the first time scientists have written genetic code for yeast. Jef Boeke, director of New York University Langone's Institute for Systems Genetics and an organizer of the project, and his colleagues synthesized their first chromosome in 2014. They dubbed their project Sc2.0 ("Sc stands for S. cerevisiae).

The new papers, however, signal an important advance. The chromosomes generated this time represent the largest amount of genetic material ever synthesized, and the new Sc2.0 cells are substantially different from their natural, or "wild type, relatives. "In addition to building the thing, we've really added new features to chromosomes that weren't there before, said Boeke.

Among the most significant of these new features is a program the scientists called "SCRaMbLE, or "Synthetic Chromosome Recombination and Modification by LoxP-mediated Evolution (scientists are congenitally disposed toward convoluted acronyms). The program allows scientists to rearrange elements within the genome to generate new and potentially useful permutations.

Whereas many of Boeke's peers labor for years in the lab trying to genetically modify organisms, the SCRaMbLE system "lets the yeast do the work and lets the yeast teach us new biology, Boeke said. It's like a version of the lottery in which you can continuously and instantaneously roll new numbers until you get a result you want.

Other innovations in the Sc2.0 genome include the removal of duplicate bits of genetic code and the addition of short genetic sequences that distinguish synthetic chromosomes from their natural counterparts.

"By rebuilding chromosomes, these teams are showing that biology can be remade such that it is easier to measure, model and manipulate, said Andrew Endy, a professor of bioengineering at Stanford University who was not involved in the project. Endy noted that evolution doesn't necessarily favor biological systems that are easy to understand; scientists have been analyzing the human genome for 25 years and still aren't really sure how a lot of it works. If researchers can engineer simpler cells - ones whose DNA the scientists wrote themselves - they will have an easier time harnessing those systems for research, medicine and industry.

Unlike other synthetic organisms, the engineered yeast is a eukaryote - a complex cell with diverse internal structures, just like the cells in the human body. It has more genetic material than the bacteria synthesized by the Venter Institute and Harvard projects.

Yeast is among the most well-studied organisms on Earth, a staple of biology labs, making it extremely useful for research. …

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