Scientists manage to combine human muscle genes into yeast cells

• Scientists have combined human muscle genes with yeast cells
• Yeast and human cells are very similar
• This process should provide a helpful method of studying how things like cancer develop in the human body

The DNA of baker's yeast has been successfully altered by biotechnologist Pascale Daran-Lapujade and her team at Delft University of Technology. A vital human trait has been successfully transplanted into a yeast cell for the first time.

Humans cannot survive without a group of ten genes that Daran-group Lapujade added to yeast cells. These genes hold the instructions for a metabolic pathway that breaks down sugar to generate energy and create cellular building blocks within muscle cells. The modified yeast might be helpful in medical research because this mechanism involves various diseases, including cancer.

"Now that we understand the full process, medical scientists can use this humanized yeast model as a tool for drug screening and cancer research," Daran-Lapujade says.

It turns out human cells are pretty similar to yeast cells

According to Daran-Lapujade, there are a lot of similarities between yeast and a human being: “It seems weird since yeast lives as single cells and humans consist of a substantially more complex system, but the cells operate in a very similar way.”

Therefore, scientists frequently introduce human genes into yeast. Researchers may study one mechanism in a pure environment because yeast eliminates all other interactions that might occur in the human body.

“As compared to human cells or tissues, yeast is a fantastic organism for its simplicity to grow and its genetic accessibility: its DNA can be easily modified to address fundamental questions,” Daran-Lapujade explains. “Many pivotal discoveries such as the cell division cycle were elucidated thanks to yeast.”

Making a human-yeast hybrid

Previously, Daran-group Lapujade successfully created synthetic chromosomes that serve as a DNA platform for adding new activities to yeast. They aimed to determine whether the cells could still function as a whole after integrating multiple human genes and whole metabolic pathways.

“What if we take the same group of genes that controls the sugar consumption and energy production of human muscles into yeast?” Daran-Lapujade wondered. “Can we humanize such an essential and complex function in yeast?”

Francine Boonekamp and Ewout Knibbe, two Ph.D. students and co-first authors, found that creating a humanized yeast was surprisingly easy.

“We didn’t just transplant the human genes into yeast; we also removed the corresponding yeast genes and completely replaced them with the human muscle genes", Daran-Lapujade explained. “You might think that you cannot exchange the yeast version with the human one because it’s such a specific and tightly regulated process both in human and yeast cells. But it works like a charm!”.

This could lead to further humanized yeasts

Using lab-grown human tissue cells, the researchers collaborated with Professor Barbara Bakker's lab at the University Medical Centre Groningen to examine the expression of human genes in yeast and their natural human muscle milieu. The novel humanized yeast is valuable as a model for human cells because of the striking similarities between the properties of human enzymes produced in yeast and their original human cells.

This particular mechanism is but a minor portion of human metabolism, however. Humanized yeasts might be used to study numerous additional processes in human and yeast cells that are analogous to this one.

Even though Daran-Lapujade concentrates on the theoretical and technical elements of engineering yeast and does not intend to investigate the usage of the humanized yeast herself, she intends to work with other researchers who are considering using the tool.

“This is just the starting point,” she says, “we can humanize yeast further and step by step build up a more complex human environment in yeast,” she added.

You can view the study in its entirety in the journal Cell Reports.

Study abstract:

"Although transplantation of single genes in yeast plays a key role in elucidating gene functionality in metazoans, technical challenges hamper humanization of full pathways and processes. Empowered by advances in synthetic biology, this study demonstrates the feasibility and implementation of full humanization of glycolysis in yeast. Single gene and full pathway transplantation revealed the remarkable conservation of glycolytic and moonlighting functions and, combined with evolutionary strategies, brought to light context-dependent responses. Human hexokinase 1 and 2, but not 4, required mutations in their catalytic or allosteric sites for functionality in yeast, whereas hexokinase 3 was unable to complement its yeast ortholog. Comparison with human tissues cultures showed preservation of turnover numbers of human glycolytic enzymes in yeast and human cell cultures. This demonstration of transplantation of an entire essential pathway paves the way for establishment of species-, tissue-, and disease-specific metazoan models."