Long chain fatty acids (LCFA) constitute a particular class of lipids whose developmental roles are coming under increasing scrutiny. These LCFAs not only have important cell specific functions but their dysregulation also forms the underlying cause of several lipid based disorders. Fatty acids are elongated in vivo by multi-enzymatic machinery in a stepwise manner. The first step of this process is carried out by a family of enzymes, conserved from yeast to humans, known as Elongases (Elos). It has been suggested that Elos work independently to elongate a fatty acid to a distinct length and perform distinct functions. Work in different species has implicated Elos in different biological roles such as barrier function, fertility, behavior and lipid homeostasis, but our understanding of the precise roles of these elongases in fatty acid elongation and how it relates to their physiological roles is not very well understood. To better understand the functions of Elos, I have characterized all Drosophila elongases for their developmental roles. In this thesis, I have shown that Drosophila elongases that are more conserved across species have more important functions (eg viability) as compared to the less conserved elongases. More specifically, I have discovered an elongases, sit still (sits), disruption of which in the nervous system results in striking locomotor and behavior defects, as well as decreased lifespan. I have also characterized another elongase, baldspot, which is important for imparting the epidermal barrier function in Drosophila, a conserved function of elongases across species. By elucidating the in vivo functions of these two Drosophila elongases, this work provides insight into the developmental roles of Elos and their links to diseases such as psoriasis, icthyosis, macular degeneration, Adrenoleukodystrophy (ALD) and Multiple Sclerosis (MS).
| Identifer | oai:union.ndltd.org:wpi.edu/oai:digitalcommons.wpi.edu:etd-dissertations-1537 |
| Date | 29 January 2014 |
| Creators | Gupta, Prachi |
| Contributors | Joseph B. Duffy, Advisor |
| Publisher | Digital WPI |
| Source Sets | Worcester Polytechnic Institute |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Doctoral Dissertations (All Dissertations, All Years) |
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