Research

Things we are focusing on

CRISPR-Cas

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.

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Retrotransposon

Retrotransposons (RTs) are known to be encoded by a wide range of genetic elements in both eukaryotes and prokaryotes, and play a dominant role in genomic evolution.  Those systems usually consist of an RNA intermediate and a multi-functional protein with reverse transcription and endonuclease activities, and jump by a “copy and paste” mechanism in genome. Crucially, about 47% of human genome is derived from RTs. Our group is interested in site-specific RTs including bacterial RNA intron and eukaryotic non-LTRs. We aim to biochemically and structurally understand those jumping machineries in DNA genome, and develop novel bio-tools for DNA manipulation.

Functional LncRNAs

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.

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