- B.S., Microbiology, Shandong University, China, 1996
- Ph.D., Genetics, Institute of Microbiology, Chinese Academy of Sciences, 1999
- Postdoc., Yale University
Ciliogenesis and Intraflagellar Transport in Chlamydomonas and C. elegans
I am interested in ciliogenesis and intraflagellar transport (IFT). Cilia/flagella, including primary cilia and sensory cilia, are highly conserved organelles that project from the surface of many cells. Cilia play important roles in the cell biology and physiology of an organism. Dysfunctional cilia can lead to several human diseases, including polycystic kidney disease (PKD), retinitis pigmentosa and Bardet-Biedl syndrome (BBS). The assembly and maintenance of flagella is dependent on a motility process occurring underneath the flagellar membrane called intraflagellar transport (IFT). IFT is a microtubule dependent transport system, which moves non-membrane-bound particles from the cell body out to the tip of the cilium/flagellum, and then returns them to the cell body. We study this process by using model organisms of biflagellate green alga Chlamydomonas reinhardtii and small round worm Caenorhabditis elegans. Chlamydomonas is an excellent model system for the biochemical and molecular –genetic analysis of proteins and processes that occur in flagellum. C. elegans, on the other hand, is a model system that is amenable to easy mutational analysis of genes and has sixty sensory neurons that have various morphologically distinct types of sensory cilia at the distal end of their dendrites. Currently, the lab is focused on:
1) Characterizing IFT particle proteins
IFT particles are protein complexes composed of at least 17 different peptides. Although IFT is thought to be a transportation system, the role of each IFT particle component has not been studied extensively. It is quite possible that some of them are involved in cargo specificity and some of them are involved in integrating signals from other processes. To explore these possibilities, we cloned several new IFT genes from Chlamydomonas and will characterize each of them in detail.
2) Understanding how IFT is regulated.
IFT is a precisely regulated process. IFT particle must load and unload its cargo and change its motor at two turning points, the flagellar base and tip. So far it is little known about how IFT is regulated. We will use cell biological, biochemical and genetic approaches to identify proteins that play a role in regulating IFT.
3) Understanding how IFT is involved in ciliary sensory function.
The membranes of all eukaryotic motile (9 +2) and immotile primary (9 +0) cilia harbor channels and receptors involved in sensory transduction. These receptors are transported from the cytoplasm onto the ciliary membrane by targeted exocytosis of vesicles to a point adjacent to the ciliary basal body. We demonstrated that select GFP-tagged sensory receptors, once in the ciliary membrane, undergo rapid vectorial transport along the entire length of the cilia of Caenorhabditis elegans sensory neurons. This motility is disrupted in certain IFT mutants. Our current focus on this project is to further characterize this membrane protein movement and understand its role in ciliary sensory function.