- Bachelor, University of Science and Technology of China, China
- PhD, Institute of Molecular and Cell Biology, Singapore
- Assistant Professor, School of Biological Sciences, NTU, Singapore, 2010
- Post-doctoral research fellow, Harvard Medical School/Immune Disease Institute, USA, 2006
- Post-doctoral research fellow, Institute of Molecular and Cell Biology, Singapore, 2004
A mammalian cell is crowdedly filled with many membrane bound organelles, which, like organs in our bodies, are structural units that are able to carry out specific cellular functions. As the knowledge of human organs is essential for the understanding of our body, studying cellular organelles would similarly help us to understand the biology of a cell. Our lab is interested in the dynamic organization of organelles and how it is determined by the membrane and membrane bound proteins. To achieve that end, we are utilizing cutting edge imaging technology in combination with biochemistry and molecular biology techniques.
The role of Arl small GTPases on Golgi structure and function
Golgi apparatus or complex is consisting of a tightly stacked flatten membrane sacs, called cisternae. In secretory pathway, protein and lipid cargos exiting the ER sequentially transit through cis, medial, trans Golgi and trans-Golgi network (TGN), during which cargos acquire specific modifications at each region. At TGN, cargos are sorted into membrane carriers (vesicles or tubules etc.) destined for endosome, lysosome or plasma membrane. The TGN also receive membrane carriers from endosomes. Although Golgi was discovered more than 100 years ago and is currently intensively researched, the molecular mechanism behind the structure and function of Golgi is still obscure. To gain insight of this organelle, we are studying Golgi localized small GTPases by taking advantage of the fact that small GTPases always serve as the most important nodes of the signaling networks.
The biogenesis of nuclear envelope and nuclear pores
ER Tubule adhesion/ ER sheet wrapping/
prepore model pore insertion model
Nuclear envelope (NE) is a special ER membrane sheet that tightly surrounds interphase chromatin mass. The NE is consisting of two layers of membrane which are separated by a luminal space and only fuse or connect at nuclear pores. A giant protein complex, called nuclear pore complex (NPC), is assembled at each pore. NPC has a molecular weight of 60-120 MD and its enormous size is achieved by 8-fold symmetrical repeats of ~ 30 nucleoporins (Nups). During mitosis, both the NE and NPCs disassemble at the end of prophase and re-assemble at late anaphase around the chromosome mass. One of the fundamental questions fascinating cell biologists is the biogenesis of NE and NPCs, which currently remains unclear. The ER tubule adhesion/prepore model is generally accepted in this field for the reassembly of NE and NPCs. However, based on multiple imaging approaches, we recently proposed the ER sheet wrapping/pore insertion model for mitotic biogenesis of NE and NPCs. We are currently investigating the detailed molecular events during the formation of mitotic NE and NPCs.
The dynamics of the endoplasmic reticulum (ER)
In mammalian cells, the ER is the largest membranous organelle and has a massive network of membrane tubules (high curvature) and sheets. The ER tubules form polygonal network at the peripheral of cells, while sheets are mainly localized near the nucleus. The ER is a highly dynamic and very complex organelle. Many interesting questions remained to be explored about the ER at molecular and cellular levels. We are trying to address the following two questions. 1) How do membrane curvatures contribute to the biological functions of the ER, such as protein and lipid biosynthesis, secretion and calcium storage? 2) There are various functional domains of the ER, such as transitional ER (which is the starting point of secretion), nuclear envelope, rough and smooth ER. How are these domains generated and maintained?