Our research focuses on several aspects of DNA replication and gene
transcription using methods of crystallography and other biochemistry
and biophysics.
Human mitochondrial DNA polymerase has been
implicated in drug toxicity of antiviral drugs designed against HIV
reverse transcriptase. We use structures of human
mitochondrial DNA polymerase as a guide for designing more potent
and less toxicity antiviral reagents.
Gene expression system in mitochondria shows a
clear viral origin: The mitochondrial RNA polymerase
active site domain resembles that of T7 bacteriophage. However, mitoRNA
polymerase differs from T7 RNA polymerase by functionally depending
on transcription factors. Studies of mitochondrial
transcription not only provides us important links between human
diseases and gene expression defects, but also an valuable
point on evolution of transcription systems.
T7 RNA polymerase is a major tool for
RNA synthesis in vitro. We are working on reengineering the
polymerase to gain various new functions for generation of modified
RNA.