MSGID: 1:317/3 63e476f0   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    'We're not all that different': Study IDs bacterial weapons that could   
   be harnessed to treat human disease    
    Discovery of ancient immune-fighting machinery paves way toward more   
   'CRISPR'-like technologies    
      
     Date:   
         February 8, 2023   
     Source:   
         University of Colorado at Boulder   
     Summary:   
         When it comes to fighting off invaders, bacteria operate in a   
         remarkably similar way to human cells, possessing the same core   
         machinery required to switch immune pathways on and off, according   
         to new research.   
      
      
         Facebook Twitter Pinterest LinkedIN Email   
   FULL STORY   
   ==========================================================================   
   When it comes to fighting off invaders, bacteria operate in a remarkably   
   similar way to human cells, possessing the same core machinery required   
   to switch immune pathways on and off, according to new University of   
   Colorado Boulder research.   
      
      
   ==========================================================================   
   The study, published Feb. 8 in the journal Nature, also sheds light   
   on how that shared, ancient machinery -- a cluster of enzymes known as   
   ubiquitin transferases -- works.   
      
   Better understanding, and potentially reprogramming this machine,   
   could ultimately pave the way to novel approaches for treating a host of   
   human diseases, from autoimmune disorders like Rheumatoid arthritis and   
   Crohn's disease to neurodegenerative diseases like Parkinson's disease,   
   the authors said.   
      
   "This study demonstrates that we're not all that different from bacteria,"   
   said senior author Aaron Whiteley, an assistant professor in the   
   Department of Biochemistry. "We can learn a lot about how the human body   
   works by studying these bacterial processes."  The next CRISPR?  The study   
   is not the first to showcase the lessons bacteria can teach humans.   
      
   Mounting evidence suggests that portions of the human immune system   
   may have originated in bacteria, with evolution yielding more complex   
   iterations of bacterial virus-fighting tools across plant and animal   
   kingdoms.   
      
   In 2020, University of California Berkeley biochemist Jennifer Doudna   
   won the Nobel Prize for CRISPR, a gene-editing tool that repurposes   
   another obscure system bacteria use to fight off their own viruses,   
   known as phages.   
      
   The buzz around CRISPR ignited renewed scientific interest in the role   
   proteins and enzymes play in anti-phage immune response.   
      
   "Over the past three to five years people have realized it doesn't end   
   with CRISPR. The potential is so much bigger," said Whiteley.   
      
   Missing link in evolutionary history For the study, Whiteley and   
   co-first author Hannah Ledvina, a Jane Coffin Childs Postdoctoral   
   Fellow in the department, collaborated with University of California   
   San Diego biochemists to learn more about a protein called cGAS (cyclic   
   GMP-AMP synthase), previously shown to be present in both humans and,   
   in a simpler form, bacteria.   
      
   In bacteria and in humans, cGAS is critical for mounting a downstream   
   defense when the cell senses a viral invader. But what regulates this   
   process in bacteria was previously unknown.   
      
   Using an ultra-high-resolution technique called cryo-electron microscopy   
   alongside other genetic and biochemical experiments, Whiteley's team took   
   an up-close look at the structure of cGAS's evolutionary predecessor in   
   bacteria and discovered additional proteins that bacteria use to help   
   cGAS defend the cell from viral attack.   
      
   Specifically, they discovered that bacteria modify their cGAS using a   
   streamlined "all-in-one version" of ubiquitin transferase, a complex   
   collection of enzymes that in humans control immune signaling and other   
   critical cellular processes.   
      
   Because bacteria are easier to genetically manipulate and study than   
   human cells, this discovery opens a new world of opportunity for research,   
   said Ledvina.   
      
   "The ubiquitin transferases in bacteria are a missing link in our   
   understanding of the evolutionary history of these proteins."  Editing   
   proteins The study also revealed just how this machine works, identifying   
   two key components -- proteins called Cap2 and Cap3 (CD-NTase-associated   
   protein 2 and 3) -- which serve, respectively, as on and off switches   
   for the cGAS response.   
      
   Whiteley explained that in addition to playing a key role in immune   
   response, ubiquitin in humans can serve as a sort of marker for   
   cellular garbage, directing excess or old proteins to be broken down and   
   destroyed. When that system misfires due to mutations in the machine,   
   proteins can build up and diseases, such as Parkinson's, can occur.   
      
   The authors stress that far more research is needed but the discovery   
   opens exciting scientific doors. Just as scientists adapted the ancient   
   bacterial defense system CRISPR into scissor-like biotechnology that   
   can snip mutations out of DNA, Whiteley believes pieces of the bacterial   
   ubiquitin transferase machine -- namely Cap3, the "off switch" -- could   
   ultimately be programmed to edit out problem proteins and treat disease   
   in humans.   
      
   He and his team, with the help of Venture Partners at CU Boulder, have   
   already filed for intellectual property protection, and they're moving   
   forward with more research.   
      
   "The more we understand about ubiquitin transferases and how they evolved,   
   the better equipped the scientific community is to target these proteins   
   therapeutically,"Whiteley said. "This study provides really clear evidence   
   that the machines in our body that are important for just maintaining   
   the cell started out in bacteria doing some really exciting things."   
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Human_Biology # Immune_System # Infectious_Diseases   
                   # Lymphoma   
             o Plants_&_Animals   
                   # Bacteria # CRISPR_Gene_Editing #   
                   Biotechnology_and_Bioengineering # Biology   
       * RELATED_TERMS   
             o Immune_system o Great_Ape_language o Pathogen o T_cell o   
             HIV o Transplant_rejection o Adult_stem_cell o White_blood_cell   
      
   ==========================================================================   
   Story Source: Materials provided by   
   University_of_Colorado_at_Boulder. Original written by Lisa   
   Marshall. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Hannah E. Ledvina, Qiaozhen Ye, Yajie Gu, Ashley E. Sullivan,   
      Yun Quan,   
         Rebecca K. Lau, Huilin Zhou, Kevin D. Corbett, Aaron T. Whiteley. An   
         E1- E2 fusion protein primes antiviral immune signalling in   
         bacteria. Nature, 2023; DOI: 10.1038/s41586-022-05647-4   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/02/230208191716.htm   
      
   --- up 49 weeks, 2 days, 10 hours, 50 minutes   
    * Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)   
   SEEN-BY: 15/0 106/201 114/705 123/120 153/7715 226/30 227/114 229/110   
   SEEN-BY: 229/111 112 113 114 307 317 400 426 428 470 664 700 292/854   
   SEEN-BY: 298/25 305/3 317/3 320/219 396/45   
   PATH: 317/3 229/426