Esther Holt

Multiple sclerosis (MS) is a common neurodegenerative disease and involves the demyelination of axons within the central nervous system. Usually in less severe stages, these axons will become remyelinated. Myelin is formed by oligodendrocytes, and this process is regulated by various lipid signaling molecules. One of the known signaling lipids is lysophosphatidic acid (LPA), which is involved in initiation of the formation of myelin membrane extensions. LPA is made from the action of autotaxin enzymes on lysophosphatidylcholine. However, previous studies have not fully defined the location within the cell that LPA is formed nor how its interactions promote myelination. My research aims to further define these locations and interactions of autotaxin and LPA using fluorescent autotaxin probes. These probes will enable imaging of the activity of autotaxin during oligodendrocyte differentiation without impairing its enzymatic ability, which will give us further mechanistic insight on how these lipids influence myelination. Two probes will be synthesized with varying fluorescence capability and will allow for tracking of their activity and location within cells. Once, the probes have been synthesized and characterized they will be evaluated for their performance to determine which probe provides enhanced fluorescent imaging ability. The defined probe and conditions will be applied to primary cultures of rodent oligodendrocyte precursor cells (OPCs). These cells are commonly used as models of myelination and these studies will allow us to gain further insight into autotaxin activity and LPA involvement in membrane formation and growth in OPCs.