The CRISPR–Cas modules are adaptive immune systems present in archaea, bacteria and even giant viruses that provide sequence-specific protection against invasive DNA or RNA. In addition to their microbial functions, RNA-guided DNA binding and cutting have proven to be transformative tools for genome and epigenome editing across wide-ranging cell types and organisms. Despite extensive effort, limited types of CRISPR-Cas nucleases currently provide the foundation for this revolutionary technology with known deficiencies, such as big molecular size and off-target editing. Our group utilizes metagenomic analysis of microbial communities to discover novel Cas proteins. Together with in vitro test, structural determination and optimization and in vivo test, we aim to develop novel bio-tools for RNA and DNA manipulation which offer advantages beyond the existing technologies.
LncRNAs were previously assumed to be non-functional by-products of transcription and therefore overlooked as a powerful biomolecular tool. Emerging evidence affirms that lncRNAs play important roles in cell behavior. A thorough structural understanding of these lncRNAs in their physiological complexes is crucial to elucidating their mode of action, but conformational flexibility and limitations in experimental tools have prevented the determination of any high-resolution structures. Our research goal is to set up an innovative, reproducible, and robust platform for the 3D structural analysis of functional lncRNA complexes by combining advanced biochemistry, cell biology and cryo-EM technologies.