Researchers Provide New Insights on CRISPR-Cas proteins
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Researchers Provide New Insights on CRISPR-Cas proteins

Researchers at the University of Georgia and UConn Health have discovered a new adaptation process in CRISPR-CAS Proteins that could lead to the formulation of new biological applications to ward off attacks from invading viruses.

CRISPR-CAS, short for Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated is a single defense mechanism that exists around various bacteria and archaea. Scientists have been studying this system to further understand how it develops immunity from viruses with the hope of replicating its mechanism to edit defective genes that place humans at risk of diabetes and cancer.

In a nutshell, viruses attack bacteria and create a record of various DNA replications – each bearing tiny pieces of various invaders. Consequently, the bacteria utilize the defective DNA to make RNAs that bind with a bacterial protein causing the viral DNA to die.

In the past, researchers did not understand how the cell recognized virus invaders nor which bacteria bear the necessary proteins that develop immunity.

With this research, scientists were able to identify “how the bacterial immune system creates a molecular memory to remove harmful viral DNA sequence and how this passed down to the bacterial progeny,” says Brenton Graveley.

Basic Protein Production

Professor Michael Terns, a principal investigator of the project says that the research is focusing on how CISPR-CAS proteins adapt to different DNA fragments and integrate into the host genome. “This is just one of the many first steps to determine basic biological processes in CISPR-CAS proteins that could build immunity of future generations from viruses.”

The researchers at the University of Georgia created several strains of archaeal organisms with key genetic deletions for the experiments. On the other hand, Tern’s research team captured DNA fragments in the CRISPR loci which were then sent to the Graveley lab in Farmington. Using an Illumina MiSeq system, scientists captured and sequence hundreds of different DNA strains and derived data for supercomputing and interpretation.

Looking at the data, researchers have noted unique patterns about how two previously poorly characterized Cas4 proteins bind with Cas1 and Cas2 proteins in the CRISPR-Cas system.

The CRISPR-Cas proteins function like an army in the human’s immune system. Within these proteins are several tiny protein sections like Cas1 and Cas2. When the latter binds with two other proteins called Cas4-1 and Cas4-2, they signal other protein fragments to control the virus-carrying DNAs and send them in another direction where they are ultimately destroyed.

According to Terns, the mechanism of Cas4 proteins remain mysterious at this point but they know that they are responsible for leading the process.

Terns and Graveley laboratory will continue their collaboration to provide more insights on CRISPR-Cas proteins. The research derives fund from the NIH R35 grant which has helped both labs discover this unique CRISPR-Cas protein adaptation.

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