Maxwell
Sutherl

Biochemistry REU The loss of Ahcy family proteins do not lead to premature retinal degeneration in Drosophila melanogaster.

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Authors:

Maxwell Sutherl

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The eye is a high oxygen-consuming tissue because of phototransduction processes in the retina leading to oxidative stress. Oxidative stress is associated with an increased risk for ocular disease and disruption of epigenetic mechanisms in the eye. Methionine metabolism is important for combating oxidative stress via its role in antioxidant biosynthesis, and is necessary for all methylation reactions by producing S- adenosylmethionine (SAM) and breaking down S-adenosylhomocysteine (SAH). In this study, we used Drosophila melanogaster to determine if the knockdown of the essential enzyme, Adenosylhomocysteinase (Ahcy), and its noncanonical enzymes Adenosylhomocysteinase-like 1 (AhcyL1) and Adenosylhomocysteinase-like 2 (AhcyL2) leads to premature retinal degeneration in young flies. Ahcy is a homotetramer that functions in methionine metabolism to break down SAH. When SAM-dependent methyltransferases transfer a methyl group from SAM, they generate SAH, which inhibits methyltransferase activity. Without Ahcy, SAH accumulates inhibiting methylation reactions. To test if these enzymes are important for ocular health, we used the GAL4 UAS binary expression system that will knock down target genes at the mRNA level. We paired this Gal4 UAS system with a tissue-specific driver to knock down the target genes solely in the eye of the adult fly. We then imaged using optic neutralization to visualize the ommatidia and rhabdomeres, which are the functional optical unit of the compound eye. This live fly imaging technique enables us to characterize healthy or degenerating rhabdomeres. We found the knockdown of Ahcy, AhcyL1, and AhcyL2 showed no premature retinal degeneration when assessed through the presence or absence of rhabdomeres.

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Purdue University / 2023

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Maxwell Sutherl

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