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Scientists Build Yeast With Artificial DNA (axios.com)11
Alison Snyder reports via Axios:For more than 15 years, scientists have worked to build a complex cell with an entire genome built from scratch. This week they announced a major milestone: They've created synthetic versions of the 16 chromosomes in a yeast cell and successfully combined some of them in one cell. The feat is revealing new information about fundamental processes in cells, and it is a key step toward some scientists' vision of creating programmable cellular factories to produce biofuels, materials, medicines and other products.
The changes researchers made to yeast chromosomes fall into three main categories: increasing stability of the genome, repurposing codons (genetic sequences that carry instructions for reading DNA or RNA) and introducing a system that allows scientists to make millions of cells, each with different genetic properties. "A big problem is a lot of the things you want to make are actually toxic to the cells," [says Benjamin Blount, a synthetic biologist at the University of Nottingham in the U.K. and co-author of some of the scientific papers in a series published this week in Cell and Cell Genomics detailing the work]. With the system that reshuffles the genome and effectively mimics evolution, scientists can make many variants of yeast and pick the ones "that are really good at growing in the presence of what you're trying to make." Then, they're able to look at what's happened to their genomes to enable that particular strain to grow and make the desired product, and use that genetic information to develop strains of yeast suited for an industrial process.
The chromosomes still have to be combined in one cell that can survive, which means they have to be "basically indiscernible" from natural chromosomes in terms of the cell's fitness, Blount says. That required a lot of debugging of the genome, similar to what's done for computer code. One team was able to combine multiple chromosomes in one cell and it survived and reproduced, demonstrating a mechanism for bringing them together. Building the genomes -- and seeing when the cell doesn't work as expected as the result of one change or another -- has revealed fundamental information about genome biology, Blount says. For example, the team identified sequences in genes that interrupted a key process in the cell and led to mitochondria dysfunction, which is involved in some human diseases.
The changes researchers made to yeast chromosomes fall into three main categories: increasing stability of the genome, repurposing codons (genetic sequences that carry instructions for reading DNA or RNA) and introducing a system that allows scientists to make millions of cells, each with different genetic properties. "A big problem is a lot of the things you want to make are actually toxic to the cells," [says Benjamin Blount, a synthetic biologist at the University of Nottingham in the U.K. and co-author of some of the scientific papers in a series published this week in Cell and Cell Genomics detailing the work]. With the system that reshuffles the genome and effectively mimics evolution, scientists can make many variants of yeast and pick the ones "that are really good at growing in the presence of what you're trying to make." Then, they're able to look at what's happened to their genomes to enable that particular strain to grow and make the desired product, and use that genetic information to develop strains of yeast suited for an industrial process.
The chromosomes still have to be combined in one cell that can survive, which means they have to be "basically indiscernible" from natural chromosomes in terms of the cell's fitness, Blount says. That required a lot of debugging of the genome, similar to what's done for computer code. One team was able to combine multiple chromosomes in one cell and it survived and reproduced, demonstrating a mechanism for bringing them together. Building the genomes -- and seeing when the cell doesn't work as expected as the result of one change or another -- has revealed fundamental information about genome biology, Blount says. For example, the team identified sequences in genes that interrupted a key process in the cell and led to mitochondria dysfunction, which is involved in some human diseases.
