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 Brittany  Dudley

Brittany Dudley

Brittany Dudley

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Advisor : Charles Chalfant

Program

MS

Ceramide synthases (CerS) are a group of enzymes in sphingolipid metabolism, which catalyze the formation of ceramide by acylation of free primary amine group of sphingosine or dihydrosphingosine. Ceramide is synthesized in the Golgi, and then transported from the ER and to the Golgi apparatus or lysosomes by these enzymes in the endoplasmic reticulum (ER) by ceramide transfer protein (CERT) or by passive vesicular trafficking. Within these organelles, ceramide can be phosphorylated by CERK, thereby resulting in the formation of ceramide 1-phosphate (C1P). This bioactive lipid is responsible for a multitude of biological processes, including inflammation, cell survival and proliferation. There are six different isoforms of CerS, each corresponding to specific sphingoid chain lengths. The goal of our study is to discern the anabolic CerS responsible for producing the substrate ceramide utilized by CERK to produce C1P. In this regard, selective down regulation of each of these enzymes, it can be deduced which isoform has the primary role in synthesizing C1P. Furthermore, the absence of a particular isoform results in a compensation phenomenon within sphingolipid and eicosanoid synthesis, which may prove to further our knowledge in the exact location and purpose of these downstream metabolites.