Transcription and Gene Regulation
Bin Liu, PhD
Transcription is the first and central step of gene expression, in which the DNA template is copied into RNA by the RNA polymerase (RNAP); thus defects in transcription and its regulation can lead to a variety of severe human diseases, including cancer. However, the lack of the structures of many more key complexes has hindered the understanding of the detailed mechanisms. Our long-term goal is to provide a structural basis for understanding the mechanisms of transcription initiation, elongation and termination by the bacterial RNAP.
We shall study the transition of transcription from initiation to termination phases, the regulation of different transcription stages by various factors and the mechanisms by which RNAP translocates with nucleotide addition in bacteria, including E. coli and selected pathogenic bacteria, such as Helicobacter pylori. These objectives will be achieved by structural determination of the RNAP in complex with functionally associated factors and appropriate DNA or RNA substrates captured at various steps in the processes, using cryo-electron microscopy and X-ray crystallography, as well as by appropriate biochemical experiments.
The information gained from our proposed research will greatly advance the understanding of all cellular transcription processes, benefit the development of novel antibiotics, and pave the way for discovering novel therapeutic directions and targets for transcription-related diseases.
In the meantime, we also have strong interests in determining the structures of other biologically important and disease-related (including cancer-related) cellular macromolecular complexes.