Building Human Muscle Genes in the DNA of Baker’s Yeast

Biotechnologist Pascale Daran-Lapujade and also her team at Delft College of Technology managed to construct human muscle genes in the DNA of baker’s yeast. This is the 1st time researchers have successfully placed such a vital human feature into a yeast cell. Their research was released in Cell Reports.

The feature that Daran-Lapujade’s lab included to yeast cells is governed by a group of ten genes that humans can not survive without; they contain the blueprint for a so-called metabolic pathway– a process that breaks down sugar to catch the power and construct cellular building blocks inside muscle cells. This procedure plays a role in many diseases such as cancer, meaning that the changed yeast could serve as a device in medical study. “Now that we understand the complete process, medical scientists can use this humanized yeast model as a tool for drug testing and cancer research,” Daran-Lapujade says.

Human and yeast are similar

According to Daran-Lapujade, there are a lot of similarities between a yeast and a human being: “It appears strange since yeast live as single cells and also humans consist of a substantially more complex system. However, the cells operate in a very similar form.” Therefore it is quite typical in science to transplant human genes in a yeast. Because scientists can get rid of all other interactions there might be in the human body, yeast supplies a clean environment where they can examine just one process.

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

Humanized yeast

Previously, Daran-Lapujade’s team succeeded in engineering artificial chromosomes that function as a DNA system for building brand new functions into yeast. From there, they wanted to observe how far they could go with including multiple human genes and whole metabolic pathways and if the cells would still function as a whole. “What if we take the same team of genes that controls the sugar consumption and power production of human muscles into yeast?” Daran-Lapujade wondered. “Can we humanize such an important and complex work in yeast?”

With surprising ease, Ph.D. students and co-1st authors Francine Boonekamp and Ewout Knibbe were able to engineer a humanized yeast. “We did not just transplant the human genes into yeast. We also deleted the corresponding yeast genes and completely replaced them with the human muscle genes,” Daran-Lapujade describes. “You might think that you can not exchange the yeast version with the human one because it is such a specific and tightly regulated process both in human and yeast cells. Nevertheless, it functions like a charm.”

Humanizing further

The researchers have worked with Professor Barbara Bakker’s lab (University Medical Center Groningen), where they can compare the expression of human genes in yeast and their native human muscle environment, utilizing lab-grown human tissue cells. The properties of human enzymes created in yeast and in their native human cells were remarkably similar, supporting the value of the brand new humanized yeast as models for human cells.

This one process is just a tiny part of the human metabolism; there are many more similar procedures between yeast and human cells that can be examined in humanized yeasts. While Daran-Lapujade focuses on the fundamental and also technological aspects of engineering yeast and thus does not plan to examine applications of the humanized yeast herself, she hopes to collaborate with other scientists interested in using the tool. “This is just the beginning point,” she states, “we can humanize yeast further, also step by step build up a more complex human environment in yeast.“

Reference:

Francine J. Boonekamp et al, Full humanization of the glycolytic pathway in Saccharomyces cerevisiae, Cell Reports (2022). DOI: 10.1016/j.celrep.2022.111010

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