The CRISPR-Cas gene system offers huge potential value for the treatment of hereditary diseases. The CRISPR gene base and Cas proteins provide adaptive immunity in prokaryotes against invading bacteriophages and plasmids. As a response, phages also evolved anti-CRISPR proteins that counteract and overcome this immunization route.
In the past 5 years, Dr. Jia concentrated on the immune mechanisms in Prokaryotes against invasive bacteriophages and plasmids. With methods that combine genetics, biochemistry, structural biology, and more, she revealed the elusive principles governing target RNA cleavage, regulation of DNase cleavage activity, and autoimmunity suppression to defend against invasive bacteriophages by type III CRISPR-Csm systems. In addition, she has elucidated an anti-CRISPR mechanism that a phage-encoded anti-CRISPR enables complete evasion of type VI CRISPR-Cas13 immunity. Further, her work has provided insights into an essential initial step of crRNA-guided DNA integration by a nuclease-deficient Cascade-TniQ complex. These fundamental molecular mechanisms provided the key structural information, unlocking the potential for the optimization and development of CRISPR-Cas gene editing tools.
Dr. Jia continues to elucidate the mechanism of the phage-bacteria arm race mysteries with the goal to facilitate the development of antimicrobial agents and biotechnology tools with potential medical and therapeutic implications. One of her recent discoveries has clarified the molecular mechanisms of the CRISPR-Caspase mediated antiphase defense, holding the potential to develop RNA-activated CRISPR-protease tools. Her studies on molecular mechanisms offer further insight into the functions of various proteins in CRISPR-Cas systems that facilitate the development and expansion of CRISPR-Cas, toolbox, and deep mining of the potential of CRISPR-Cas as gene editing tools.
Currently, her research focuses on molecular mechanisms of the interaction between the host cells and the intruding viruses, bacteria, and other microorganisms by using technologies in biochemistry, molecular biology, microbiology, and structural biology, to provide a theoretical basis not only for the treatment of resistant bacterial infections but also for the development of antiviral drugs and new biotechnology tools.