An article presents fresh perspectives on PARIS, a defense mechanism that bacteria deploy against viral threats.
For many years, researchers at Montana State University have delved into distinctive immune systems, and a team from the Department of Microbiology and Cell Biology has made significant progress, as detailed in a paper recently released in the prestigious journal Nature.
On August 7, the team published a paper titled “A virally-encoded tRNA neutralizes the PARIS antiviral defense system,” which was prioritized for publication due to its critical findings. The lead author, doctoral student Nate Burman, collaborated with professor Blake Wiedenheft, as well as six other MSU scientists along with their partners from France, Russia, and Sweden.
This research investigates the PARIS immune system, a tool that bacteria utilize to defend against viral infections. The PARIS, or Phage Anti-Restriction Induced System, expands upon Wiedenheft’s ongoing investigations into CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. Wiedenheft is considered a leading global expert in this area.
“CRISPRs are part of a broader family of adaptive immune systems in bacteria, but researchers have adapted these systems into programmable molecular tools, which are currently being used to mend damaged DNA for essential therapies,” stated Burman, who is entering his third year of doctoral studies. “However, CRISPRs aren’t the sole immune systems in bacteria. What sets PARIS apart is its ability to identify viral proteins rather than nucleic acids. This is reminiscent of how the human immune system operates. While PARIS is fundamentally different from the human immune system, the conceptual similarities are fascinating.”
A key revelation from the paper is the first complete visualization of the PARIS system’s structure. To achieve this, Burman employed a specialized ultra-high-powered microscope located at MSU. This advanced equipment is rare among universities nationwide and was introduced to MSU’s Cryo-EM Core Facility in 2021, making MSU only the second university in the area to obtain it.
“With the cutting-edge cryo-electron microscope at MSU, Nate could observe the PARIS complex within a bacterial cell,” remarked Wiedenheft. “It’s astonishing that we can now look inside cells and witness the machinery responsible for sustaining life and defending against infections.”
The structure of PARIS is characterized by a propeller-like formation that uses ATP (adenosine triphosphate) for energy to locate invading viral proteins. When it identifies foreign proteins, it triggers the release of a toxin that halts viral replication, thereby safeguarding healthy cells.
Burman noted that there are various PARIS immune systems that function differently, and future research will focus on uncovering the triggers that activate these systems. Understanding how PARIS detects viral threats and initiates a defense could enhance comprehension of immunity mechanisms not only in bacteria but also in other organisms.
As the research group in Wiedenheft’s lab continues to advance in structural biology, Burman highlighted the institutional backing for their work, which has created a collaborative environment for scientists across all career stages. Burman’s journey in Bozeman commenced during his undergraduate years at Carroll College in Helena, where he took part in a research experience for undergraduates (REU) at MSU. Currently, he values the chance to mentor emerging scientists following in his footsteps.
“Blake’s support has been invaluable, pushing us to think broadly about small proteins, their roles in nature, and potential new applications,” Burman added.
