Approaches for genetic manipulation of Naegleria fowleri

福氏耐格里虫的基因操作方法

• 批准号: 10641130
• 负责人: JAMES Culvin MORRIS
• 金额: $ 19.06万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-09 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10641130
• 关键词: Ablation; Address; Alleles; Amoeba genus; Area; Awareness; Basic Science; Binding; Biology; Brain; CRISPR/Cas technology; Categories; Cell Line; Classification; Detection; Development; Drug Targeting; Gene Expression; Gene Silencing; Gene Transfer Techniques; Generations; Genes; Genetic; Goals; Infection; Invaded; Life; Mediating; Molecular; Mutagenesis; Naegleria; Naegleria fowleri; National Institute of Allergy and Infectious Disease; Nose; Organism; Outcome; Parasites; Pathogenicity; Pathway interactions; Pharmacotherapy; Phenotype; Process; Proteins; RNA Interference; Reaction; Reagent; Resistance; Technology; Therapeutic; Therapeutic Agents; Transgenic Organisms; Validation; Work; chemical genetics; contaminated water; drug development; drug discovery; druggable target; fighting; gene function; genetic approach; genetic manipulation; inhibitor; interest; knockout gene; loss of function; mortality; novel strategies; novel therapeutics; overexpression; pathogen; primary amebic meningoencephalitis; promoter; targeted treatment; therapeutic target; tool; transgene expression; vector

Project Summary The goal of this proposal is to develop molecular tools and approaches for the study of the pathogenic free-living amoeba Naegleria fowleri. These currently do not exist. This amoeba is the causative agent of primary amebic meningoencephalitis (PAM), an almost invariable lethal brain infection. The lack of useful drugs for the treatment of this infection emphasizes the need to develop better therapeutic agents for amoebae infections. The lack of understanding of gene function in the parasite remains a major hurdle in target-based drug development campaigns. Here, we propose to address this problem by developing approaches for gene silencing and ablation by RNAi and CRISP/Cas9-mediate gene editing and transgene expression. These approaches will serve as an important first step in understanding both gene function and essentiality, key to early-stage drug discovery efforts.

项目总结