Carvalho Teresa Gil, Ménard Robert
Unité de Biologie et Génétique du Paludisme, Institut Pasteur, 75724 Paris Cedex 15, France.
Curr Issues Mol Biol. 2005 Jan;7(1):39-55.
Genome manipulation, the primary tool for assigning function to sequence, will be essential for understanding Plasmodium biology and malaria pathogenesis in molecular terms. The first success in transfecting Plasmodium was reported almost ten years ago. Gene-targeting studies have since flourished, as Plasmodium is haploid and integrates DNA only by homologous recombination. These studies have shed new light on the function of many proteins, including vaccine candidates and drug resistance factors. However, many essential proteins, including those involved in parasite invasion of erythrocytes, cannot be characterized in the absence of conditional mutagenesis. Proteins also cannot be identified on a functional basis as random DNA integration has not been achieved. We overview here the ways in which the Plasmodium genome can be manipulated. We also point to the tools that should be established if our goal is to address parasite infectivity in a systematic way and to conduct refined structure-function analysis of selected products.
基因组操作是确定序列功能的主要工具，对于从分子层面理解疟原虫生物学和疟疾发病机制至关重要。近十年前报道了疟原虫转染的首次成功。自那时起，基因靶向研究蓬勃发展，因为疟原虫是单倍体，且仅通过同源重组整合DNA。这些研究为许多蛋白质的功能带来了新的认识，包括疫苗候选物和耐药因子。然而，许多必需蛋白质，包括那些参与寄生虫侵入红细胞的蛋白质，在没有条件诱变的情况下无法进行表征。由于尚未实现随机DNA整合，蛋白质也无法基于功能进行鉴定。我们在此概述疟原虫基因组可被操作的方式。我们还指出，如果我们的目标是以系统的方式解决寄生虫感染性问题，并对选定产物进行精细的结构-功能分析，应该建立哪些工具。
