IDENTIFICATION OF DIFFERENTIATION MUTANTS IN TOXOPLASMA GONDII

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 人类病原体弓形虫是分布最广的原生动物寄生虫之一，感染了大约三分之一的世界人口。弓形虫作为免疫受损个体中威胁生命的机会性疾病的原因而臭名昭著。弓形虫在人和中间宿主体内的无性复制以两种形式为特征：快速生长的‘速殖子’和潜伏的‘缓殖子’组织包囊，这两种形式都是疾病传播和病因所必需的。速殖子是急性疾病和先天性神经出生缺陷的罪魁祸首，而分裂较慢的缓殖子可能终生潜伏在组织中，对免疫功能低下的患者构成持续威胁。速殖子和缓殖子之间的相互转换过程是寄生虫生存和致病的核心，但在遗传水平上仍然知之甚少。为此，我们最近开发了一种基因筛查，以确定控制寄生虫分化的调控基因，并分离出在分化条件下无法转化为慢性体的突变体。最近，我们已经成功地扩大了突变体的生产，在这里，我们建议对这些突变体进行表征，并利用它们来定义调节缓殖子分化的遗传途径，并分离参与这一过程的必要基因。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The human pathogen Toxoplasma gondii is one of the most widely distributed protozoan parasites infecting approximately one-third of the world's population. T. gondii has achieved notoriety as a cause of life-threatening opportunistic disease in immunocompromised individuals. Asexual replication of T. gondii in humans and intermediate hosts is characterized by two forms: rapidly growing 'tachyzoites' and latent 'bradyzoite' tissue cysts both of which are essential for disease propagation and causation. Tachyzoites are responsible for acute illness and congenital neurological birth defects, while the more slowly dividing bradyzoite can remain latent within tissues life-long, presenting a continual threat to immunocompromised patients. The interconversion process between tachyzoites and bradyzoites is central to the parasite's survival and pathogenicity, yet it remains poorly understood at the genetic level. To this end we have recently developed a genetic screen to identify regulatory genes that control parasite differentiation and have isolated mutants that fail to convert to bradyzoites under differentiation conditions. Recently we have successfully scaled up the production of mutants and here we propose to characterize these mutants and use them to define genetic pathways that regulate bradyzoite differentiation and to isolate essential genes involved in this process.