Research Terms
Life Sciences Biochemistry Physical Sciences Chemistry
Research Interest
The Li laboratory is working to uncover the molecular mechanisms of two RNA-mediated processes: the CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated) immunity and ribosome synthesis. The CRISPR-Cas systems confer immunity to bacteria and archaea against invading viruses through several novel enzymatic processes such as RNA-guided DNA or RNA cleavage, RNA-stimulated second messenger synthesis and degradation, and second messenger-stimulated RNA cleavage. Ribosome is the RNA-protein machine that synthesizes proteins in all organisms. The maturation pathway of ribosome is mediated by RNA-guided RNA modification and processing and is thus a target for anticancer drugs. The Li lab uses structural biology (x-ray crystallography and electron cryomicroscopy, or cryoEM), directed protein evolution, yeast genetics, and other biophysical methods to elucidate the chemical basis for these fascinating enzymes and to provide synthetic strategies in development of gene editing, liquid biopsy, virus detection and therapeutic biotechnology.
The COVID-19 Pandemic demonstrated the need for rapid, affordable, and accurate virus testing methods. While the standard Polymerase Chain Reaction (PCR)-based methods remain effective and widely used, they require hours to complete and are unable to directly detect virus variants and other subtle changes to genetic material. Additionally, PCR lacks the possibility for testing under limited resources.
MORIARTY (an acronym for Multipronged, One-pot, RNA-Induced, Affordable, Rapid, Test sYstem) is an enzyme-based method that can detect nucleic acids from a variety of sources, including the SARS-CoV2 coronavirus, seasonal flu varieties, and circulating tumor DNA for early cancer detection. This detection method is consistent with the accuracy of PCR methods but is considerably faster does not require costly equipment, with results available in as little as 15 minutes.
The technology utilizes CRISPR-Cas enzymes to detect genetic material and induce a fluorescent signal. The system can be easily repurposed and reprogramed for any genetic material detection, including viral RNA, viral DNA, and ctDNA, and can be used to detect variants with single-nucleotide resolution. This fidelity, for example, can detect the difference between the various coronavirus variants with the same point-of-care test. It can also be used for liquid biopsies to test for ctDNA for various cancers.