Exploring the function of a novel tyrosine kinase like (TKL) protein in Toxoplasma endodyogeny

探索新型酪氨酸激酶样 (TKL) 蛋白在弓形虫内生过程中的功能

• 批准号: 10451021
• 负责人: Rajshekhar Gaji
• 金额: $ 20万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-03 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10451021
• 关键词: Acute; Affect; Attenuated; Biogenesis; Biology; Blindness; Cell Cycle; Cell division; Cells; Child; Complement; Complex; Cytokinesis; Cytoplasm; Cytosol; Data; Daughter; Defect; Development; Electron Microscopy; Elements; Encephalitis; Enzymes; Eukaryota; Event; Family; Genes; Goals; Immunofluorescence Immunologic; Impaired cognition; Impairment; In Vitro; Individual; Infection; Inflammation; Life; Life Cycle Stages; Light; Lytic Phase; Mammalian Cell; Mass Spectrum Analysis; Membrane; Microscopy; Microtubules; Mitosis; Monitor; Morphology; Newborn Infant; Parasites; Parents; Pathogenesis; Pathology; Phase; Phosphotransferases; Play; Pregnant Women; Process; Protein Family; Protein Tyrosine Kinase; Proteins; Regulation; Research; Role; Shapes; Signal Pathway; Signal Transduction; Spontaneous abortion; Testing; Tissues; Toxoplasma; Toxoplasma gondii; Toxoplasmosis; Vacuole; Virulence; Virulence Factors; Work; abortion; attenuation; daughter cell; effective therapy; fitness; human pathogen; in vitro Assay; member; mouse model; mutant; novel; novel therapeutics; pathogen

PROJECT SUMMARY/ABSTRACT Toxoplasma gondii is an important human pathogen that divides by a unique mode of cell division called endodyogeny that is quite distinct from binary fission that occurs in mammalian cells. Since Toxoplasma division is divergent from higher eukaryotes, a better understanding of this complex process and identification of its key components and their mode of regulation would potentially open doors for selective strategies to disrupt infection. TgTKL4 is a member of tyrosine kinase like (TKL) family protein in Toxoplasma that localizes to parasite cytoplasm with its expression mainly confined to synthesis (S), mitosis/cytokinesis (M/C) phases of the cell cycle. Interestingly, loss of this kinase causes defects in cell division that results in misshapen parasites with compromised fitness and attenuated virulence. Specifically, TgTKL4 null mutants with abnormal morphology display significant defects in in vitro propagation suggesting loss of this kinase affects one or more stages of Toxoplasma lytic cycle. Since TgTKL4 is a cell-cycle regulated kinase and parasites deficient in this enzyme show abnormal shape, we hypothesize that this kinase is a part of the signaling network that dictates parasite morphology during endodyogeny. To further understand the role of this novel TKL kinase in parasite replication, we propose to: (1) Identify substrates of TgTKL4; and (2) Determine the role of TgTKL4 in Toxoplasma endodyogeny. Thus, our proposed work will help us understand the precise function of TgTKL4 and signaling network associated with this kinase during cell division that determines parasite morphology.

项目总结/文摘