The Mechanism of Genetic Exchange in Trichomonas vaginalis

描述（由申请人提供）：虽然阴道毛滴虫是世界上最常见的非病毒性性传播感染，但我们对其最基本的生物学过程的了解仍然存在很大差距。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，然而目前的数据表明遗传交换是可能发生的。虽然滴虫病通常无症状，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，对这种寄生虫感染采取更好的治疗方案可能会降低患严重疾病的风险。基因交换的概念是特别相关的，因为我们考虑到它的含义，对甲硝唑，治疗阴道毛滴虫症状感染的药物选择耐药性上升。本研究利用广泛的样本收集和综合、多维的方法，旨在阐明阴道毛滴虫的基因交换机制，这将对这一常见疾病的控制和治疗具有重大意义。为了验证阴道绦虫能够进行基因交换的假设，我们提出：鉴定从遗传混合感染中自然产生的重组；2)。分析临床分离的大量寄生虫的倍性，鉴定杂交种，以确定自然界中通过减数分裂或拟性过程重组的可能性；3)。研究阴道毛滴虫减数分裂特异性基因的调控、表达和功能，因为这些基因在所有生物中都被证明在减数分裂或副性过程中起严格的作用，并对它们进行了深入的研究。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，而且还为利用遗传杂交的可能性打开了大门，遗传杂交是一种具有巨大潜力的强大工具，可用于促进分子研究，并开始阐明极其复杂的阴道毛滴虫基因组组装。

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.