Many biological processes are carried out by complex, multi-component macromolecular assemblies.  The assembly and dynamics of these molecular machines has been central to structural and cell biology, and has imposed tremendous challenges owing to their unusual complexity.  The research in this lab aims to understand the structural basis of assembly, dynamics and function of molecular complexes by using X-ray crystallography and electron cryo-microscopy as primary techniques.  Our current research is focused on viruses and bacterial injectisome.

DNA packaging/translocation is crucial in assembly and infection of many double-stranded DNA (dsDNA) viruses such as bacteriophages T7 and P22 and herpesvirus.  The DNA packaging is achieved at a unique vertex of the viral capsid by a molecular motor consisting of the portal and terminase complex, which cleaves monomeric units from concatemeric viral DNA and pumps DNA into the capsid in an ATP-dependent manner.  The translocation of viral DNA from within the capsid into the host cell in bacteriophages such as T7 and P22 involves a series of precisely controlled molecular events, fulfilled by several virally encoded proteins.  The molecular mechanisms of DNA packaging and translocation in herpesvirus and dsDNA bacteriophage are being investigated by means of X-ray crystallography and electron cryo-microscopy.

Many Gram-negative pathogenic bacteria employ a complex protein secretion system termed type III secretion system (TTSS) to transport bacterial effector proteins across three membrane barriers into eukaryotic host cytoplasm.  The effector proteins delivered by TTSS are capable of modulating and interfering with the host cellular processes, which cause diseases in animals and plants such as plague, typhoid fever, bacterial dysentery.  The TTSS is composed of more than 20 structural proteins, effector proteins, and chaperones.  Our structural investigation targets the major structural components, the needle complex and the translocon, of TTSS in Shigella flexneri.

We combine X-ray crystallography and electron cryo-microscopy to investigate structures of large moleular assemblies at intermediate to atomic resolution.