G6PD Deficiency-Induced Hemolysis
And the challenge for Malaria Eradication
G6PD Deficiency weakens the cell through the decreased ability to produce NADPH, but does not directly cause hemolysis External oxidizing triggers, such as Primaquine, cause hemolysis in G6PD deficient individuals |
Malaria causes G6PDd to be more prevalent in a population because weakened blood cells confer some protection against infection by malarial parasites
Primaquine is an antimalarial, and the only antimalarial that is effective enough to prevent relapse. |
Though the G6PD gene is well-conserved in many model organisms, I will be using zebrafish as a model organism to conduct my experiment. G6PD deficient zebrafish and humans share similar phenotypes when triggered by external factors, and hemolysis is easy to observe in zebrafish due to their transparent nature [8]. In addition, zebrafish are relatively inexpensive with shorter generation times, compared to other common model organisms.
Throughout my study, I will be comparing the methylation patterns and NADPH levels of male, nonpregnant female, and pregnant (egg-producing) zebrafish. |
Initial Fluorescent Spot Test followed by CRISPR/CAS9 to knockout well conserved methylation.
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Hypothesized result of knockout
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Bisulfite Sequencing of Pregnant, G6PD deficient zebrafish
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Hypothesized result
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TAP-MS of control (methylated) and treatment (unmethylated) groups
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Hypothesized Results
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G6PD deficiency is currently a major obstacle for malaria eradication. One way this could be overcome is through pharmacogenomics. Pharmacogenomics is assessing an individual's genes to determine their likely drug response, and treat accordingly, with different drugs or dosages for the same condition, depending on one's genetics [9]. The chemical screen conducted in Aim 2 would be the perfect launchpad to begin creating different drugs that could be taken in tandem with, or instead of, Primaquine for G6PD deficient individuals who contract malaria.
Additionally, if I had to add a fourth aim, I would have like to look at how the post-translational modifications may change depending on methylation levels, and whether that would have an effect on level of NADPH production. Namely, I would have looked at phosphorylation sites, as they are the most common functional group that alters protein folding.
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