The overwhelmingly homochiral nature of life has left a puzzle as to whether mirror-image biology systems based on a chirally inverted version of molecular machinery could also exist. We initially developed a proof-of-concept mirror-image genetic replication and transcription system based on a synthetic 174-aa mirror-image African swine fever virus polymerase X (ASFV pol X), followed by a more efficient and thermostable 352-aa mirror-image Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) that led to the realization of mirror-image PCR, gene transcription, reverse transcription, as well as mirror-image DNA and RNA sequencing. Toward building a mirror-image ribosome, we realized the assembly of mirror-image 5S ribonucleoprotein complexes, protein translation without aminoacyl-tRNA synthetases, and ribozyme-catalyzed mirror-image tRNA charging. More recently, we chemically synthesized a 90-kDa high-fidelity mirror-image Pfu DNA polymerase, enabling the accurate assembly of a kilobase-sized mirror-image gene and biostable storage of an entire paragraph of digital text in mirror-image DNA. Our work is a small step toward establishing the mirror-image central dogma of molecular biology. It also highlights the potential to exploit mirror-image biomolecules as a unique class of therapeutic and informational tools.
BIO
Ting Zhu received his B.E. from the Department of Engineering Mechanics at Tsinghua University, M.S. from the Department of Mechanical Engineering at MIT (advisor: Roger Kamm), Ph.D. from the Harvard-MIT Division of Health Sciences and Technology (advisor: Jack Szostak), and postdoctoral training from the Department of Earth, Atmospheric and Planetary Sciences at MIT and Department of Molecular Biology at Massachusetts General Hospital (advisors: Maria Zuber and Gary Ruvkun). He joined the School of Life Sciences at Tsinghua University in 2011.
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