Defining the novel eukaryotic biology of the Apicomplexan plastid

描述（由研究者提供）：顶复合体寄生虫含有一种称为顶质体的基本质体细胞器。鉴于其独特的特征，顶质体是这些寄生虫中新型真核生物的来源，也是药物和疫苗开发的潜在阿喀琉斯之踵。利用顶质体独特的生物学特性进行治疗开发的挑战在于确定可靶向的特定途径和功能。我的总体目标是阐明顶质体在两种重要人类病原体中的新途径和功能：全球主要传染病杀手疟原虫和威胁输血血液供应的新出现的人类感染巴贝斯虫寄生虫。在迈向这一目标的重要一步中，我最近证明了血期恶性疟原虫顶质体的唯一基本功能是类异戊二烯的生物合成

DESCRIPTION (provided by investigator): Apicomplexan parasites contain an essential plastid organelle called the apicoplast. Given its unique features, the apicoplast is a source of novel eukaryotic biology in these parasites and a potential Achilles' heel for drug and vaccine development. The challenge in taking advantage of the apicoplast's unique biology for therapeutic development has been to identify the specific pathways and functions that can be targeted. My overall goal is to elucidate the novel pathways and functions of the apicoplast in two important human pathogens: Plasmodium spp parasites, a leading global infectious disease killer, and Babesia spp parasites, an emerging human infection that threatens the transfusion blood supply. In an important step towards this goal, I recently demonstrated that the sole essential function of the apicoplast in blood-stage P. falciparum is the biosynthesis of isoprenoid precursor, IPP. As such, P. falciparum parasites that have completely lost their apicoplast can be rescued by supplementation with IPP. Significantly, chemical rescue of "apicoplast(-)" parasites enables new approaches and novel experiments as outlined in this application. I investigate several novel aspects of apicoplast biology: 1) identification of protein factors required for a critical and unique step during protein import into the apicoplast, 2) identificatio of the small molecule isoprenoids derived from IPP that likely have essential cellular functions in P. falciparum, and 3) determination of the function of the apicoplast in Babesia parasites, which share important pathogenic and evolutionary features with P. falciparum. The scope of these aims allows a thorough investigation of the novel features of the Apicoplexan apicoplast that will yield fascinating eukaryotic biology and promising therapeutic targets.