近日，诺丁汉大些生物学院的科学家们与莱斯特大学，牛津大学，帝国理工大学和荷兰莱顿大学在国际杂志《PLoS Pathogens》上共同发表了他们的研究成果。科学家们依靠寄生虫生命周期中一个新蛋白的发现，锁定了战胜全球毁灭性疾病疟疾的新目标。
研究揭示了在疟疾寄生虫有性繁殖阶段中的一个重要角色。它可以证明新治疗方法能够有效阻止其轨道上的疾病。
咬回去
疟疾是一种破坏性的全球性疾病。每年有数百万的临床病例和接近一百万人死于此病。疟疾是由血红细胞的感染和被称为疟原虫的一个微小的寄生虫而引起的。疟原虫有四个重要物种。这些生物体由疟蚊在人与人之间传播。当疟蚊叮了一个受感染人以后，它吮吸血液中含有的寄生虫，然后通过叮咬可传播给下一个受害者。
带领研究学者并参与诺丁汉大学生物学院基因组学和遗传学中心Tewari博士小组的David Guttery博士说：“疟疾寄生虫是一个复杂的有机体，了解它是如何繁殖是阻止其传播疾病的关键。我们的研究已经确认了细胞分裂周期基因在疟原虫和它在男性生殖细胞发展中的作用。因此它是阻止疟原虫繁殖的“刹车”。 我们发现如果去除该基因，雄配子不能形成和分裂出他们的宿主细胞（称为exflagellation进程）。阻断这些细胞的形成将会是一个在预防疟疾由蚊子传播到哺乳动物的重要战略。”
新目标
确认的蛋白被称为CDC20，在伯氏疟原虫（在鼠类间传染）的细胞分裂周期中发挥作用。这种基因显示在学多器官的细胞分裂中都发挥着重要作用，但是到目前为止，其在疟疾寄生虫上的作用还不得而知。新的研究对CDC20在疟原虫细胞分裂和疟疾寄生虫雄性细胞(microgametes)生长中的作用首次进行了描述。这种雄性细胞是寄生虫在人与蚊子之间传播的基础。科学家们发现缺乏这种基因的雄性细胞将停止迸发出其宿主细胞和与雌性细胞受精。
疟疾寄生虫生命周期中的受精阶段发生在蚊子吮吸感染了疟疾的血液之后。在此期间，雄性细胞前体（小配子体）快速复制的DNA产生8个雄性细胞（配子）。这些配子在一个被称为exflagellation的过程中衍生出小配子体，并寻找雌性细胞进行受精。通过阻止exflagellation这个进程，研究小组确定了一种中断疟疾传播的方法。
这个研究小组的成员来自诺丁汉大学，牛津大学，帝国理工大学，莱顿大学，莱斯特大学和由MRC资助的国家医学研究所，威康信托基金和EviMalar。
诺丁汉大学的成员在之前的研究中发现了在疟疾寄生虫生命周期中的其他重要因素。（生物谷Bioon.com）
doi:10.1371/journal.ppat.1002554
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A Putative Homologue of CDC20/CDH1 in the Malaria Parasite Is Essential for Male Gamete Development
David S. Guttery1, David J. P. Ferguson2, Benoit Poulin1, Zhengyao Xu1, Ursula Straschil3, Onny Klop4, Lev Solyakov5, Sara M. Sandrini1, Declan Brady1, Conrad A. Nieduszynski1, Chris J. Janse4, Anthony A. Holder6, Andrew B. Tobin5, Rita Tewari1,3*
Cell-cycle progression is governed by a series of essential regulatory proteins. Two major regulators are cell-division cycle protein 20 (CDC20) and its homologue, CDC20 homologue 1 (CDH1), which activate the anaphase-promoting complex/cyclosome (APC/C) in mitosis, and facilitate degradation of mitotic APC/C substrates. The malaria parasite, Plasmodium, is a haploid organism which, during its life-cycle undergoes two stages of mitosis; one associated with asexual multiplication and the other with male gametogenesis. Cell-cycle regulation and DNA replication in Plasmodium was recently shown to be dependent on the activity of a number of protein kinases. However, the function of cell division cycle proteins that are also involved in this process, such as CDC20 and CDH1 is totally unknown. Here we examine the role of a putative CDC20/CDH1 in the rodent malaria Plasmodium berghei (Pb) using reverse genetics. Phylogenetic analysis identified a single putative Plasmodium CDC20/CDH1 homologue (termed CDC20 for simplicity) suggesting that Plasmodium APC/C has only one regulator. In our genetic approach to delete the endogenous cdc20 gene of P. berghei, we demonstrate that PbCDC20 plays a vital role in male gametogenesis, but is not essential for mitosis in the asexual blood stage. Furthermore, qRT-PCR analysis in parasite lines with deletions of two kinase genes involved in male sexual development (map2 and cdpk4), showed a significant increase in cdc20 transcription in activated gametocytes. DNA replication and ultra structural analyses of cdc20 and map2 mutants showed similar blockage of nuclear division at the nuclear spindle/kinetochore stage. CDC20 was phosphorylated in asexual and sexual stages, but the level of modification was higher in activated gametocytes and ookinetes. Changes in global protein phosphorylation patterns in the Δcdc20 mutant parasites were largely different from those observed in the Δmap2 mutant. This suggests that CDC20 and MAP2 are both likely to play independent but vital roles in male gametogenesis.
