The Liang Laboratory is focused on integrating the power and advantages of different imaging system modalities, including those using electrons, x-rays and visible lights, to scrutinize how macromolecular machineries function in various biological processes in real time and at unprecedented resolution. Capitalizing on breakthroughs in detector technology and image processing algorithms, Liang laboratory is particularly interested in using cryo-electron microscopy (cryo-EM) as a primary tool to visualize macromolecular complexity. Cryo-EM is especially well suited for molecular systems traditionally challenging for structural characterization, including membrane proteins and large and heterogeneous assemblies. In addition, we employ x-ray crystallography and fluorescence light microscopy to provide complementary structural and dynamic information for challenging systems of significant biological importance.
One such challenging system is the RNA synthesis machinery of a class of pathogenic and sometimes deadly non-segmented negative-sense (NNS) RNA viruses, including Rabies, Measles, Ebola, Marburg, Respiratory Syncytial Virus (RSV) and human Parainfluenza Virus (HPIV). Central to the life of these viruses is RNA synthesis, which is carried out by the RNA polymerase (the multifunctional enzyme). The structural basis of the RNA synthesis machinery remains largely unclear.
The Liang laboratory is dedicated to understanding the structure and function of the RNA synthesis machinery of RSV and HPIV, the top two leading causes of severe pediatric respiratory tract diseases worldwide. The RNA synthesis by the RNA polymerase of these viruses is essential for viral pathogenesis in infants and children. The Liang laboratory will establish a RNA synthesis platform for RSV and HPIV, elucidate how this RNA synthesis machine functions, and identify potential antiviral therapeutic targets for more effective treatment. Our immediate research goal would be to decipher the molecular architecture of the RNA synthesis machineries of these viruses using cryo-EM and x-ray crystallography. This could lead to the development of effective antiviral drugs to block the RSV and HPIV activity. Such drugs would result in a substantial reduction in serious RSV and/or HPIV infections in infants and children and provide a major achievement for human health.