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Author: Donna Huber

Discovery of repurposing drug candidates for the treatment of diseases caused by pathogenic free-living amoebae

Diseases caused by pathogenic free-living amoebae include primary amoebic meningoencephalitis (Naegleria fowleri), granulomatous amoebic encephalitis (Acanthamoeba spp.), Acanthamoeba keratitis, and Balamuthia amoebic encephalitis (Balamuthia mandrillaris). Each of these are difficult to treat and have high morbidity and mortality rates due to lack of effective therapeutics. Since repurposing drugs is an ideal strategy for orphan diseases, …

Resistance to some, but not other dimeric lindenane sesquiterpenoid esters is mediated by mutations in a Plasmodium falciparum esterase

Unique lindenane sesquiterpenoid dimers from Chloranthecae spp. were recently identified with promising in vitro antiplasmodial activity and potentially novel mechanisms of action. To gain mechanistic insights to this new class of natural products, in vitro selection of Plasmodium falciparum resistance to the most active antiplasmodial compound, chlorajaponilide C, was explored. In all selected resistant clones, …

Dennis Kyle: Finding Solutions for Deadly Diseases

Dennis Kyle leads the UGA Center for Tropical and Emerging Diseases, and his endowment enables him to run a 16-person lab of student researchers, postdocs, and research scientists fighting a host of parasitic diseases around the world. (Photo by Andrew Davis Tucker/UGA) GRA Endowment helps researchers save lives through drug discovery The Amoeba Summit in …

Trainee Spotlight: Melissa Sleda

  Melissa Sleda, a Ph.D. trainee is Silvia Moreno’s laboratory, is in her third year at UGA. She is originally from Sandusky, Michigan and attended Lawrence Technological University where she majored in Molecular and Cell Biology with a minor in Chemistry. At UGA, she has held positions as the Secretary for the Cell Bio Grad …

Comparative sequences of the Wolbachia genomes of drug-sensitive and resistant isolates of Dirofilaria immitis

The recent identification of isolates of D. immitis with confirmed resistance to the macrocyclic lactone preventatives presents an opportunity for comparative genomic studies using these isolates, and examining the genetic diversity within and between them. We studied the genomes of Wolbachia endosymbionts of five isolates of D. immitis maintained at the University of Georgia. Missouri and Georgia-2 are maintained as drug …

Monoclonal Antibodies Generated against Glycoconjugates Recognize Chemical Linkers

Monoclonal antibodies (mAbs) that recognize glycans are useful tools to assess carbohydrates' structure and function. We sought to produce IgG mAbs to the human milk oligosaccharide (HMO), lacto-N-fucopentaose III (LNFPIII). LNFPIII contains the Lewisx antigen, which is found on the surface of schistosome parasites. mAbs binding the Lewisx antigen are well-reported in the literature, but mAbs recognizing …

Biochemical and biophysical analyses of hypoxia sensing prolyl hydroxylases from Dictyostelium discoideum and Toxoplasma gondii

In animals, the response to chronic hypoxia is mediated by prolyl-hydroxylases (PHDs) that regulate the levels of hypoxia inducible transcription factor a (HIFα). PHD homologues exist in other types of eukaryotes and prokaryotes where they act on non-HIF substrates. To gain insight into the factors underlying different PHD substrates and properties, we carried out biochemical …

mSphere of Influence: Tweaking Organellar Purification Approaches

Diego Huet studies the organelles involved in the metabolic adaptations of the apicomplexan parasite Toxoplasma gondii. In this mSphere of Influence article, he reflects on how the paper “Absolute quantification of matrix metabolites reveals the dynamics of mitochondrial metabolism” by Chen et al. (W. W. Chen, E. Freinkman, T. Wang, K. Birsoy, and D. M. Sabatini, …

Probing the B- & C-rings of the antimalarial tetrahydro-β-carboline MMV008138 for steric and conformational constraints

The antimalarial candidate MMV008138 (1a) is of particular interest because its target enzyme (IspD) is absent in human. To achieve higher potency, and to probe for steric demand, a series of analogs of 1a were prepared that featured methyl-substitution of the B- and C-rings, as well as ring-chain transformations. X-ray crystallography, NMR spectroscopy and calculation …

p53 Hinders CRISPR/Cas9-Mediated Targeted Gene Disruption in Memory CD8 T Cells In Vivo

CRISPR/Cas9 technology has revolutionized rapid and reliable gene editing in cells. Although many cell types have been subjected to CRISPR/Cas9-mediated gene editing, there is no evidence of success in genetic alteration of Ag-experienced memory CD8 T cells. In this study, we show that CRISPR/Cas9-mediated gene editing in memory CD8 T cells precludes their proliferation after …