Biochemical and Functional Analysis of Trypanin

锥虫蛋白酶的生化和功能分析

• 批准号: 7441279
• 负责人: KENT L HILL
• 金额: $ 37.42万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2008-12-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7441279
• 关键词: Address; African; African Trypanosomiasis; Anterior; Binding; Biochemical; Blood Circulation; Blood Vessels; Cell Communication; Cell division; Cells; Cellular biology; Chlamydomonas; Cilia; Communicable Diseases; Complex; Connective Tissue; Cytokinesis; Defect; Development; Disease; Drug Delivery Systems; Dynein ATPase; Endothelium; Epilepsy; Equipment and supply inventories; Eukaryota; Eukaryotic Cell; Eye diseases; Flagella; Genes; Genomics; Goals; Greek; Hereditary Disease; Human; Human body; Hydrocephalus; In Situ; Infertility; Insect Vectors; Left; Length; Life Cycle Stages; Malaria; Mediating; Membrane; Midgut; Modeling; Molecular; Morbidity - disease rate; Morphogenesis; Movement; Mutation; Names; Neuraxis; Obesity; Organelles; Organism; Parasites; Pathogenesis; Penetration; Phenotype; Polycystic Kidney Diseases; Proteins; Proteomics; RNA Interference; Research; Role; Salivary Glands; Sensory; Signal Transduction Pathway; Site; Site-Directed Mutagenesis; Smith Magenis syndrome; Staging; Structure; Testing; Therapeutic Intervention; Thinking; Tissues; Trypanosoma; Trypanosoma brucei brucei; Tsetse Flies; cell motility; extracellular; health economics; human disease; loss of function; migration; mortality; mutant; neuronal cell body; pathogen; three dimensional structure; tomography; transmission process

African trypanosomes (e.g. Trypanosoma brucei) are protozoan parasites that cause African sleeping sickness, a fatal disease with devastating health and economic consequences. These parasites are digenetic organisms, spending part of their life cycle in a mammalian host and part in an insect vector (the tsetse fly). Trypanosomes are highly motile in both life cycle stages and motility is central to parasite development and disease pathogenesis. Motility is mediated by a single flagellum that is an essential and multifunctional organelle with critical roles in cell motility, host-parasite interaction, cell morphogenesis and cell division. Surprisingly, we know very little about the flagellar apparatus at the the molecular level. In particular, we lack an understanding of how flagellar proteins are assembled into supramolecular structures within the axoneme and how they function individually and collectively to drive cell motility and other flagellum functions. The long-term goal of the proposed research is to advance our understanding of the trypanosome flagellum and to exploit trypanosomes as a model to investigate the eukaryotic cilium. This will be done using a combination of functional and structural approaches. RNAi, site-directed mutagenesis and ultrastructural analyses will be used to investigate the function of trypanin and other components of the dynein regulatory complex (DRC). The DRC is part of a signal transduction pathway that regulates flagellar motility and is essential in bloodstream-form trypanosomes, making it a candidate drug target. The trypanosome flagellum is essentially the same as cilia and flagella in other eukaryotes, including humans. Flagella are required for motility of several human pathogens and are present on most tissues of the human body. They perform motility, transport and sensory functions. Infectious diseases caused by pathogens that require cilia include African sleeping sickness and Malaria and are responsible for mortality an morbidity in approximately 0.4 billion people world-wide. Heritable human diseases caused by cilia defects include: hydrocephalus, infertility, epilepsy, left-right axis defects, eye disorders, polycystic kidney disease and obesity. Therefore, in addition to addressing fundamental questions in cell biology, this research directly impacts efforts to understand and treat infectious diseases and genetic diseases in humans.

非洲锥虫（如布鲁氏锥虫）是引起非洲人睡眠的原生动物寄生虫