This project determines an evolutionarily conserved mechanism by which a fat-like substance (ceramide) in the cell membrane regulates motile cilia. Motile cilia are protrusions of the cell membrane that work like whips and propel cells or move fluids. They are important to clean the lung, move the early stage embryo, and circulate growth factors in the brain. The investigator's laboratory has discovered that ceramide is critical for the function of motile cilia in green algae and mammalian cells. The investigator's research will now determine the mechanism by which ceramide regulates motile cilia. An essential part of this project is the inclusion of graduate and undergraduate students and their education in evolutionarily conserved mechanisms. This education will be extended to elementary, middle, and high school level students in innovative workshops combining art and science ('Living clay' workshops and lectures at local high schools).
It is critical for the function of motile cilia that their length and timing of assembly/disassembly is tightly regulated. A critical barrier in understanding this regulation is the lack of knowledge on dynamically activated factors for cilium length regulation. Research so far has focused on the role of proteins in the regulation of cilium length, and little is known about the role of lipids in this process. The research goal is to provide knowledge on how lipids and proteins interact in an evolutionarily conserved mechanism and how modulation of lipid metabolism can be utilized to support the function of cilia. The research focus is on the interaction of the sphingolipid ceramide with glycogen synthase 3 beta (GSK3) and other ciliogenic proteins in Chlamydomonas reinhardtii (C. reinhardtii) used as bona fide model organisms. The investigator's laboratory will use state-of-the-art lipidomics and chemoproteomics approaches to determine the function of ciliogenic lipid-protein complexes. The broader impact goal is to educate students from the elementary school to the graduate school level on evolutionarily conserved biological structures and mechanisms.
