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Tag: Christopher West

Global characterization of Dictyostelium discoideum gene and protein expression changes under hypoxic conditions

Donna Huber on December 29, 2025

Background: Aerobic eukaryotes utilize O2 to oxidize metabolites and generate ATP. The response to oxygen deprivation leads to migration to locations with more favorable concentrations (aerotaxis), differentiation, metabolic reprogramming, or more global stress responses. In mammals, changes in gene expression are particularly well studied, with the involvement of the Hypoxia-Inducible Factor (HIF-1), which regulates the transcription of …

Glycoregulation of E3(SCF) ubiquitin ligases in unicellular eukaryotes

Donna Huber on December 17, 2025

Skp1 is an essential adaptor within the Skp1/Cul1/F-box (SCF) class of E3 polyubiquitin ligases that regulate protein degradation in all eukaryotes. Skp1 is also a target of a 5-enzyme glycosylation pathway in parasites and other unicellular eukaryotes. Glycosylation of Skp1 is contingent upon oxygen-dependent hydroxylation of a critical Pro residue by a homolog of the …

O-fucosylation affects abundance but not localization of select nucleocytoplasmic proteins in Toxoplasma gondii

Donna Huber on September 1, 2025

  Toxoplasma gondii is a highly successful intracellular mammalian and avian pathogen that must adapt to a wide range of intracellular and extracellular environments. A mechanism that may support this is the modification of hydroxyamino acid rich sequences of nucleocytoplasmic proteins with O-fucose. O-fucosylation of possibly hundreds of proteins is mediated by a single highly …

PfFBXO1 is essential for inner membrane complex formation in Plasmodium falciparum during both asexual and transmission stages

Donna Huber on February 7, 2025

Plasmodium species replicate via schizogony, which involves asynchronous nuclear divisions followed by semi-synchronous segmentation and cytokinesis. Successful segmentation requires a double-membranous structure known as the inner membrane complex (IMC). Here we demonstrate that PfFBXO1 (PF3D7_0619700) is critical for both asexual segmentation and gametocyte maturation. In Toxoplasma gondii, the FBXO1 homolog, TgFBXO1, is essential for the …

Novel antibodies detect nucleocytoplasmic O-fucose in protist pathogens, cellular slime molds, and plants

Donna Huber on February 6, 2025

Cellular adaptations to change often involve post-translational modifications of nuclear and cytoplasmic proteins. An example found in protists and plants is the modification of serine and threonine residues of dozens to hundreds of nucleocytoplasmic proteins with a single fucose (O-fucose). A nucleocytoplasmic O-fucosyltransferase occurs in the pathogen Toxoplasma gondii, the social amoeba Dictyostelium, and higher …

Toxoplasma chitinase-like protein orchestrates cyst wall glycosylation to facilitate effector export and cyst turnover

Donna Huber on January 29, 2025

  Toxoplasma bradyzoites reside in tissue cysts that undergo cycles of expansion, rupture, and release to foster chronic infection. The glycosylated cyst wall acts as a protective barrier, although the processes responsible for formation, remodeling, and turnover are not understood. Herein, we identify a noncanonical chitinase-like enzyme TgCLP1 that localizes to micronemes and is targeted …

The GPI sidechain of Toxoplasma gondii inhibits parasite pathogenesis

Donna Huber on September 20, 2024

  Glycosylphosphatidylinositols (GPIs) are highly conserved anchors for eukaryotic cell surface proteins. The apicomplexan parasite, Toxoplasma gondii, is a widespread intracellular parasite of warm-blooded animals whose plasma membrane is covered with GPI-anchored proteins, and free GPIs called GIPLs. While the glycan portion is conserved, species differ in sidechains added to the triple mannose core. The …

Oxygen-dependent regulation of F-box proteins in Toxoplasma gondii is mediated by Skp1 glycosylation

Donna Huber on September 20, 2024

  A dynamic proteome is required for cellular adaption to changing environments including levels of O2, and the SKP1/CULLIN-1/F-box protein/RBX1 (SCF) family of E3 ubiquitin ligases contributes importantly to proteasome-mediated degradation. We examine, in the apicomplexan parasite Toxoplasma gondii, the influence on the interactome of SKP1 by its novel glycan attached to a hydroxyproline generated …

The Toxoplasma oxygen-sensing protein, TgPhyA, is required for resistance to interferon gamma-mediated nutritional immunity in mice

Donna Huber on June 10, 2024

  As Toxoplasma gondii disseminates through its host, the parasite must sense and adapt to its environment and scavenge nutrients. Oxygen (O2) is one such environmental factor and cytoplasmic prolyl 4-hydroxylases (PHDs) are evolutionarily conserved O2 cellular sensing proteins that regulate responses to changes in O2 availability. Toxoplasma expresses 2 PHDs. One of them, TgPHYa …

The Toxoplasma gondii F-Box Protein L2 Functions as a Repressor of Stage Specific Gene Expression

Donna Huber on May 30, 2024

  Toxoplasma gondii is a foodborne pathogen that can cause severe and life-threatening infections in fetuses and immunocompromised patients. Felids are its only definitive hosts, and a wide range of animals, including humans, serve as intermediate hosts. When the transmissible bradyzoite stage is orally ingested by felids, they transform into merozoites that expand asexually, ultimately …