CAREER: Exploring novel bacterial immune systems to expand genome editing tools

This research aims to transform the future of genome editing, paving the way for new tools that could help address critical challenges in health, food security, and environmental sustainability. By exploring a recently discovered bacterial immune system, the project seeks to provide new genetic editing technologies that are simpler, more versatile, and easier to deliver to target cells. Beyond the scientific investigation, the research will support comprehensive educational and outreach activities designed to inspire learners ranging from early childhood students to advanced graduate trainees to engage with science, technology, engineering, and mathematics (STEM). Together, the project will foster a deeper understanding of gene-editing science among both specialists and the general public, ultimately broadening participation in STEM fields. This research will systematically investigate a newly identified DNA-guided, DNA-targeting bacterial system known as DdmDE, which can recognize and eliminate genetic material without relying on the distinctive genetic signatures (PAM sequences) required by CRISPR-based methods. To accomplish this, the project will conduct biochemical and structural analyses to reveal how DdmE identifies target DNA sequences and how DdmD, a partner enzyme, is recruited and activated to cut unwanted DNA. Additionally, the research will explore natural variations in the DdmE protein and develop methods to reprogram it for advanced genome editing applications. By integrating bioinformatics, biochemistry, and biophysics, the project will create a strong foundation for harnessing DdmDE as next-generation genome editing tools. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.