Person:
Kubanek, Julia

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https://hdl.handle.net/1853/71428
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School of Biological Sciences
School established in 2016 with the merger of the Schools of Applied Physiology and Biology
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    Warding Off Disease on Coral Reefs: Antimicrobial Chemical Cues and their Future in Drug Discovery
    (Georgia Institute of Technology, 2012-05-08) Kubanek, Julia
    Unlike many animals, seaweeds do not possess adaptive immune systems to ward off disease. In many cases, they produce small molecules – natural antibiotics – that prevent colonization or infection by pathogens. We have found that seaweeds produce unusual secondary metabolites against pathogen attack, including complex isoprenoid-and shikimate-derived macrolides not seen in any other organisms. Surprisingly, these natural antifungals are not distributed evenly across algal surfaces; instead they are concentrated at discrete surface patches where they provide bursts of protection at sites that may be especially vulnerable to infection due to prior wounding. Working with the Fernandez lab at Georgia Tech, we applied surface imaging mass spectrometry to intact algal surfaces to show that antifungal defenses are heterogeneously distributed, with compound concentrations high enough at localized patches to block infection. This patchy distribution may represent an optimal defense strategy, in which the most vulnerable parts of the alga are best defended. Chemical defenses of seaweeds also serve as valuable leads for pharmaceutical development. Members of one group of algal antifungal agents, the bromophycolides, exhibit potent in vitro and in vivo antimalarial activity with an unexpected mechanism of action, inhibiting growth of the malarial parasite Plasmodium falciparum at sub-micromolar concentrations. Using a molecular probe designed from the seaweed’s antifungal agent, we identified a major molecular target and drug binding mechanism within the malaria parasite that is helping guide our synthesis of novel analogs for future development.
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    A biochemical, genetic, and genomic investigation of the evolution and ecology of sexual reproduction
    (Georgia Institute of Technology, 2010-11-17) Snell, Terry W. ; Kubanek, Julia
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    Biochemical Warfare on the Reef: The Role of Glutathione Transferases in Consumer Tolerance of Dietary Prostaglandins
    (Georgia Institute of Technology, 2010-01-06) Whalen, Kristen E. ; Lane, Amy L. ; Kubanek, Julia ; Hahn, Mark E.
    Background: Despite the profound variation among marine consumers in tolerance for allelochemically-rich foods, few studies have examined the biochemical adaptations underlying diet choice. Here we examine the role of glutathione Stransferases (GSTs) in the detoxification of dietary allelochemicals in the digestive gland of the predatory gastropod Cyphoma gibbosum, a generalist consumer of gorgonian corals. Controlled laboratory feeding experiments were used to investigate the influence of gorgonian diet on Cyphoma GST activity and isoform expression. Gorgonian extracts and semipurified fractions were also screened to identify inhibitors and possible substrates of Cyphoma GSTs. In addition, we investigated the inhibitory properties of prostaglandins (PGs) structurally similar to antipredatory PGs found in high concentrations in the Caribbean gorgonian Plexaura homomalla. Principal Findings: Cyphoma GST subunit composition was invariant and activity was constitutively high regardless of gorgonian diet. Bioassay-guided fractionation of gorgonian extracts revealed that moderately hydrophobic fractions from all eight gorgonian species examined contained putative GST substrates/inhibitors. LC-MS and NMR spectral analysis of the most inhibitory fraction from P. homomalla subsequently identified prostaglandin A2 (PGA2) as the dominant component. A similar screening of commercially available prostaglandins in series A, E, and F revealed that those prostaglandins most abundant in gorgonian tissues (e.g., PGA2) were also the most potent inhibitors. In vivo estimates of PGA2 concentration in digestive gland tissues calculated from snail grazing rates revealed that Cyphoma GSTs would be saturated with respect to PGA2 and operating at or near physiological capacity. Significance: The high, constitutive activity of Cyphoma GSTs is likely necessitated by the ubiquitous presence of GST substrates and/or inhibitors in this consumer’s gorgonian diet. This generalist’s GSTsmay operate as ‘all-purpose’ detoxification enzymes, capable of conjugating or sequestering a broad range of lipophilic gorgonian compounds, thereby allowing this predator to exploit a range of chemically-defended prey, resulting in a competitive dietary advantage for this species.