MSGID: 1:317/3 64718770   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Protein-based nano-'computer' evolves in ability to influence cell   
   behavior    
      
     Date:   
         May 26, 2023   
     Source:   
         Penn State   
     Summary:   
         The first protein-based nano-computing agent that functions as a   
         circuit has been created. The milestone puts them one step closer   
         to developing next-generation cell-based therapies to treat diseases   
         like diabetes and cancer.   
      
      
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   FULL STORY   
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   The first protein-based nano-computing agent that functions as a circuit   
   has been created by Penn State researchers. The milestone puts them one   
   step closer to developing next-generation cell-based therapies to treat   
   diseases like diabetes and cancer.   
      
   Traditional synthetic biology approaches for cell-based therapies, such   
   as ones that destroy cancer cells or encourage tissue regeneration after   
   injury, rely on the expression or suppression of proteins that produce a   
   desired action within a cell. This approach can take time (for proteins   
   to be expressed and degrade) and cost cellular energy in the process. A   
   team of Penn State College of Medicine and Huck Institutes of the Life   
   Sciences researchers are taking a different approach.   
      
   "We're engineering proteins that directly produce a desired action,"   
   said Nikolay Dokholyan, G. Thomas Passananti Professor and vice chair   
   for research in the Department of Pharmacology. "Our protein-based   
   devices or nano-computing agents respond directly to stimuli (inputs)   
   and then produce a desired action (outputs)."  In a study published in   
   Science Advances today (May 26) Dokholyan and bioinformatics and genomics   
   doctoral student Jiaxing Chen describe their approach to creating their   
   nano-computing agent. They engineered a target protein by integrating   
   two sensor domains, or areas that respond to stimuli. In this case,   
   the target protein responds to light and a drug called rapamycin by   
   adjusting its orientation, or position in space.   
      
   To test their design, the team introduced their engineered protein into   
   live cells in culture. By exposing the cultured cells to the stimuli,   
   they used equipment to measure changes in cellular orientation after   
   cells were exposed to the sensor domains' stimuli.   
      
   Previously, their nano-computing agent required two inputs to produce   
   one output. Now, Chen says there are two possible outputs and the   
   output depends on which order the inputs are received. If rapamycin is   
   detected first, followed by light, the cell will adopt one angle of cell   
   orientation, but if the stimuli are received in a reverse order, then the   
   cell adopts a different orientation angle. Chen says this experimental   
   proof-of-concept opens the door for the development of more complex   
   nano-computing agents.   
      
   "Theoretically, the more inputs you embed into a nano-computing agent, the   
   more potential outcomes that could result from different combinations,"   
   Chen said.   
      
   "Potential inputs could include physical or chemical stimuli and outputs   
   could include changes in cellular behaviors, such as cell direction,   
   migration, modifying gene expression and immune cell cytotoxicity   
   against cancer cells."  The team plans to further develop their   
   nano-computing agents and experiment with different applications of the   
   technology. Dokholyan, a researcher with Penn State Cancer Institute   
   and Penn State Neuroscience Institute, said their concept could someday   
   form the basis of the next-generation cell-based therapies for various   
   diseases, such as autoimmune diseases, viral infections, diabetes,   
   nerve injury and cancer.   
      
   Yashavantha Vishweshwaraiah, Richard Mailman and Erdem Tabdanov of Penn   
   State College of Medicine also contributed to this research. The authors   
   declare no conflicts of interest.   
      
   This work was funded by the National Institutes of Health (grant   
   1R35GM134864) and the Passan Foundation.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Stem_Cells # Lung_Cancer # Lymphoma   
             o Plants_&_Animals   
                   # Cell_Biology # Molecular_Biology #   
                   Biotechnology_and_Bioengineering   
             o Matter_&_Energy   
                   # Biochemistry # Batteries # Organic_Chemistry   
             o Computers_&_Math   
                   # Computer_Science # Mobile_Computing #   
                   Spintronics_Research   
       * RELATED_TERMS   
             o Blood_transfusion o Stem_cell_treatments o Stem_cell o   
             Chemotherapy o Gene_therapy o Nutrition o Personalized_medicine   
             o Circuit_design   
      
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   Story Source: Materials provided by Penn_State. Original written by   
   Zachary Sweger. Note: Content may be edited for style and length.   
      
      
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   Journal Reference:   
      1. Jiaxing Chen, Yashavantha L. Vishweshwaraiah, Richard B. Mailman,   
      Erdem   
         D. Tabdanov, Nikolay V. Dokholyan. A noncommutative   
         combinatorial protein logic circuit controls cell orientation   
         in nanoenvironments. Science Advances, 2023; 9 (21) DOI:   
         10.1126/sciadv.adg1062   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/05/230526142234.htm   
      
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