Mechanism behind new CRISPR tool using microscopy: New Research


Cornell University researchers have discovered a new CRISPR tool that might lead to potential antiviral and tissue engineering tools in animals and plants.

Ailong Ke, the Robert J. Appel Professor of molecular biology and genetics in the College of Arts and Sciences, and Stan J.J. Brouns of the Delft University of Technology in the Netherlands conducted research on a recently found CRISPR RNA-guided Caspase system known as Craspase.

Ke’s study in this area was supported by National Institutes of Health funds and a College of Arts and Sciences New Frontier Grant. In the Science paper, Ke and Brouns are co-corresponding authors, and Hu and Sam van Beljouw of the Delft University of Technology in the Netherlands are co-first authors.

Science published the paper, “Craspase is a CRISPR RNA-guided, RNA-activated protease” on August 24. Cryo-electron microscopy images of Craspase systems were employed in this article to illustrate how they cleave to target RNA and activate protease enzymes, which can break down protein.

The experimental explanation of this new CRISPR tool

CRISPR-Cas systems are bacterial RNA-guided nucleases that break viral DNA or RNA targets in exact places to enable significant genome editing applications. Caspases are a protease family that regulates programmed cell death in animals, including humans. The discovery that caspase-like proteins can interact with CRISPR-Cas has energised the scientific community. Craspase, a new given name for CRISPR-guided caspases.

Ke explained that this link has been completely unexpected and suggests novel ways of antiviral activity in bacteria. On the contrary, if we understand all of the gizmos inside this machinery, we might employ a system like this to build myriad biotech and medicinal applications.

“These photos culminate in a high-definition molecular film,” Ke explained. “We can see how Craspase recognises an RNA target, how this activates the protease, how long the activity lasts, and what finally turns the protease activity off by observing it back and forth. Ideas start to flow in about how to harness the potential of this platform.”

The Craspase system has aroused the curiosity of co-first author Chunyi Hu, a postdoctoral fellow in Ke’s group. “There’s a lot of competition. We and our Dutch partners pooled our resources and worked around the clock to solve the challenge “Hu said. “The process has great promise because Craspase’s output is protein breakdown rather than DNA destruction.”

“With previous CRISPR tool technologies, one wonders if the enzymes we employ to alter our DNA are safe enough, if there may be collateral damage or off-targeting,” Ke explained. “We can obtain many of the same excellent therapeutic effects with Craspase without having to worry about the safety of our genome.”

Researcher’s explanation of this study

According to Ke, the study detailed in the publication also helps researchers comprehend what Craspase performs inside bacterium cells. “Our teammates’ study shown that it’s like a master switch — the proteolytic cleavage initiates a cascade of actions in the bacteria cells that finally kills them,” Ke explained. “In this investigation, we have a partial answer. We’re currently looking into it.”

This new study will also aid scientists in better understanding the parallels between programmed cell death in human cell pathways and the same mechanism in bacterial cell pathways.

“We discovered that the same collection of proteases (caspases) drive the programmed cell death pathways in both realms of life,” Ke explained. “This finding demonstrated how deeply ingrained this route is.”

In addition to delving deeper into the functional side of this technique, Ke and his colleagues will investigate the application side, which might include tissue engineering in animals and agricultural engineering. “I hope other investigators recognise the potential of this approach and participate,” Ke added. “We all think of CRISPR-guided nuclease as a tool for curing genetic illnesses, but CRISPR-guided proteases might have far-reaching implications for biology.”

Materials provided by Cornell UniversityNote: Content may be edited for style and length.

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