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Title: Regulation of motile cilia by (phyto)ceramide
Senior Personnel: Erhard Bieberich (P.I., Georgia Regents University)
Guanghu Wang (Georgia Regents University)
Ceramide is a sphingolipid that has mostly been implicated as cell signaling lipid for the
induction of apoptosis. The P.I.’s laboratory has begun, for the first time, to define its
unique and essential role in ciliogenesis. In the previous study, the P.I. has found that
ceramide is enriched in a compartment at the base of primary cilia and that the interaction
of ceramide with atypical PKC (aPKC) is critical for ciliogenesis in mammalian cells. New
data suggest that regulation of primary and motile cilia by ceramide is evolutionarily conserved
and involves phytoceramide and ceramide as determined with Chlamydomonas and ependymal cells,
respectively. Our experiments will define lipid species critical for ciliogenesis in Chlamydomonas
and mammalian cells (Aim 1), determine ceramide-interacting proteins and their function in
intraflagellar transport (IFT) and length regulation (Aim 2); and test the significance of
ceramide for cilium function in vivo using mouse models for ceramide deficiency (Aim 3). These
experiments will address the P.I.’s long-term goal to define ceramide-regulated mechanisms
that are essential for cilium biogenesis and function.
Intellectual Merit :
Primary and motile cilia are protrusions of the cell membrane with sensory and motor function,
respectively. It is still not fully understood which factors regulate ciliogenesis. The concept
that ceramide is enriched in a specialized, ciliogenic compartment and that ciliogenesis is
regulated by a ceramide-induced ciliogenic lipid-protein complex associated with this compartment
is absolutely novel and original.
Broader Impacts :
Because most mammalian cells have cilia, results from testing of the P.I.’s concept will significantly
advance our knowledge across different research fields, including embryology, neurobiology,
wound healing and biology of epithelial cells, and stem and cancer cell biology. The concept
of a ceramide-induced lipid-protein complex defines the function of this lipid in a testable
biological context (ciliogenesis). Therefore, this study opens up a new research field in
defining the biological function of lipid-protein interaction. Methods and results obtained
from this study will go beyond ceramide and will be applicable to other lipids with cell signaling
activity. The proposed study will foster the academic career of at least two graduate students
and is fully integrated into the undergraduate student programs at Georgia Regents University.
These programs encourage students from the neighboring institutions, in particular Paine College,
a community college with primarily students from minority groups, to participate in the P.I.’s
research and to explore academic careers in biosciences. In addition, the P.I. organizes art-science
workshops teaching young students of the elementary to high school level and their parents
evolutionary concepts in biology by using clay to sculpt cells and organelles.
Keywords: cilia, ceramide, sphingomyelinase, Chlamydomonas, ependymal, IFT, brain, development
Status | Finished |
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Effective start/end date | 7/1/17 → 8/31/19 |
Funding
- National Science Foundation: $228,687.00
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