The Mechanism of Genetic Exchange in Trichomonas vaginalis

阴道毛滴虫基因交换机制

• 批准号: 8529893
• 负责人: Andrew W. Gorman
• 金额: $ 3.23万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8529893
• 关键词: Agar; Alleles; Biological Assay; Biological Process; Biology; Cell fusion; Chromosomes; Coitus; Collection; Complement; Complex; DNA Binding; DNA Repair; Data; Diploidy; Disease; Drug resistance; Epidemiology; Event; Evolution; Exhibits; Flow Cytometry; Fluorescence Microscopy; Genes; Genetic; Genetic Crosses; Genetic Crossing Over; Genetic Markers; Genetic Materials; Genetic Population Study; Genetic Recombination; Genetic Variation; Genome; Genotype; Goals; HIV; HIV Infections; Haplotypes; Health; Human Papillomavirus; Hybrids; Immunoblotting; In Vitro; Incidence; Infection; Knock-out; Knowledge; Laboratories; Life Cycle Stages; Location; Low Birth Weight Infant; Meiosis; Meiotic Recombination; Methods; Metronidazole resistance; Microbe; Microsatellite Repeats; Mining; Modeling; Molecular; Molecular Genetics; Nature; Organism; Parasites; Parasitic infection; Pathogenicity; Pharmaceutical Preparations; Phenotype; Ploidies; Polyploidy; Population; Process; Property; Recombinants; Recording of previous events; Regulation; Research; Research Project Grants; Risk; Role; SPO11 gene; Sexually Transmitted Diseases; Sister; Staging; Structure; Testing; Translating; Trichomonas Infections; Trichomonas vaginalis; Virulent; Work; asexual; clinically relevant; common treatment; gene function; neglect; protein protein interaction; public health relevance; research study; sample collection; sex; tool

DESCRIPTION (provided by applicant): Although Trichomonas vaginalis is the most common non-viral sexually transmitted infection in the world, large gaps in our knowledge concerning its most fundamental biological process still remain. The current model of the Trichomonas vaginalis life cycle illustrates mitotically dividing parasites transmitted by sexual acts, however current data suggests that genetic exchange is a likely occurrence. Although trichomoniasis is often asymptomatic, infection has been implicated in an increased incidence with HIV and associated with a variety of other serious health sequelae. Therefore, better treatment options for this parasitic infection may translate into reduced risk for severe disease. The notion of genetic exchange is particularly relevant as we consider its implications in rising resistance to metronidazole, the drug of choice in treating symptomatic infection with Trichomonas vaginalis. Using an expansive sample collection and an integrative, multidimensional approach this research application aims to elucidate the mechanism of genetic exchange in Trichomonas vaginalis, which would have huge implications for the control and treatment of this common disease. To test the hypothesis that T. vaginalis is capable of genetic exchange we propose to: 1.) Identify naturally arising recombinants from genetically mixed infections; 2.) Analyze the ploidy of numerous clinically isolated parasites and identify hybrids in order to determine the possibility of recombination by meiosis or parasexual process in nature; 3.) Investigate the regulation, expression and function of meiosis specific genes in Trichomonas vaginalis, as these genes have been shown to strictly function in meiosis or parasexual processes in all organisms in which they have been studied in depth. These studies not only hold potential to redefine how we think about Trichomonas vaginalis biology, control, and treatment but also open the door to the possibility of utilizing genetic crosses, a powerful tool with great potential which can be employed to facilitate molecular studies and begin to clarify the immensely complex assembly of the T. vaginalis genome.

描述（由申请人提供）：尽管阴道毛滴虫是世界上最常见的非病毒性传播感染，但我们对其最基本的生物学过程的了解仍然存在巨大差距。目前的阴道毛滴虫生命周期模型说明了通过性行为传播的有丝分裂寄生虫，但目前的数据表明基因交换是可能发生的。尽管滴虫病通常无症状，但感染与艾滋病毒发病率增加有关，并与各种其他严重的健康后遗症有关。因此，针对这种寄生虫感染的更好的治疗选择可能会降低患严重疾病的风险。当我们考虑基因交换对甲硝唑耐药性增加的影响时，基因交换的概念尤其重要，甲硝唑是治疗阴道毛滴虫症状感染的首选药物。这项研究应用采用广泛的样本收集和综合的多维方法，旨在阐明阴道毛滴虫的遗传交换机制，这将对这种常见疾病的控制和治疗产生巨大影响。为了检验阴道毛滴虫能够进行基因交换的假设，我们建议： 1.) 鉴定来自基因混合感染的自然产生的重组体； 2.) 分析大量临床分离的寄生虫的倍性并鉴定杂种，以确定自然界中通过减数分裂或准有性过程重组的可能性； 3.) 研究阴道毛滴虫中减数分裂特异性基因的调节、表达和功能，因为这些基因已被证明在所有对其进行深入研究的生物体的减数分裂或准有性过程中严格发挥作用。这些研究不仅有可能重新定义我们对阴道毛滴虫生物学、控制和治疗的看法，而且还为利用基因杂交的可能性打开了大门，这是一种具有巨大潜力的强大工具，可用于促进分子研究并开始阐明阴道毛滴虫基因组极其复杂的组装。