Jul 22, 2019 | Updated: 09:15 AM EDT

Synthesizing Chemical-Sensing Cells from Scratch

Jul 02, 2019 09:48 AM EDT

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Synthesizing Chemical-Sensing Cells from Scratch
(Photo : OIST)

It might be hard for so many to bake a cake from scratch, and another far-reaching story is constructing an artificial cell-like system from scratch. The leader of the Science and Technology Graduate University (OIST) Nucleic Acid Chemistry and Engineering Unit, Prof. Yohei Yokobayashi, said that synthesizing cells from scratch is of fundamental essence to understand what life is.

All around the world, scientists are beginning to develop simple artificial cells that conduct some essential biological functions and that contain small strands of DNA or RNA. It has been a challenge, however, to get these snippets of genetic material to express their encoded proteins in response to precise signals.

At present, along with other researchers from OIST and Osaka University, Yokobayashi has discovered a way to make artificial cells interact with a wide range of chemicals. The group developed a riboswitch, a gene switch that senses chemical signals, that is capable of responding to histamine, a chemical compound that is naturally produced in the body. In the presence of this chemical, the riboswitch turns on a gene inside the artificial cells. As the corresponding author on a recent study in the Journal of the American Chemical Society that depicts the approach, Yokobayashi said that scientists could one day use such a system as a new way of administering medicine.

Since it is a crucial biological compound in the immune system, the researchers chose histamine as the chemical signal for their artificial cells. In the event of any hitch by someone, histamine is the likely culprit. Also, the body releases it during allergic reactions and helps defend against foreign pathogens by spurring inflammation.

Then, the team created a so-called riboswitch that would turn this signal detection into action, mainly translating a gene to produce a protein. Usually, cells produce proteins when templates made of messenger RNA (mRNA) bind to cellular structures called ribosomes. Here, the scientists used the histamine aptamer to design a riboswitch that alters the shape of the mRNA upon binding histamine. In the absence of histamine, the form of the mRNA prevents the ribosome from binding, and no protein is produced. However, histamine-bound mRNA allows ribosome to bind and synthesize proteins.

With a collaboration with senior author Professor Tomoaki Matsuura and graduate student Yusuke Seike of the Department of Biotechnology at Osaka University, the two put the cell-free riboswitch created by Yokobayashi's team into lipid vesicles to create artificial cells. The team from Osaka attached the riboswitch to a gene expressing a fluorescent protein, so that when histamine activates the riboswitch, one that makes nanometer-scale pores on the cell membrane. When the aptamer sensed histamine, a fluorescent compound encapsulated in the vesicles was released out of the cells through the pores, modeling how the system would issue a drug.

With technology in the early stages of development, the team will make artificial cells more sensitive to a smaller amount of histamine. 

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