Developing a Transposon-based Toolkit for Genetic Analysis of Malaria Parasites

说明（由申请人提供）：疟疾是人类死亡和疾病的主要原因，每年造成4 -6亿临床疟疾病例和2- 300万死亡。控制和治疗疟疾的传统措施正变得越来越无效，迫切需要开发新的药物和疫苗。基因组研究和其他高科技进步已经产生了关于疟疾寄生虫的丰富信息；然而，利用这些信息对疟原虫基因组进行功能分析受到了基因操纵疟疾寄生虫能力有限的阻碍。我们正在开发疟疾寄生虫的高通量全基因组突变筛选技术，使用一种高效的基于转座子的寄生虫转化方法。我们建议开发该系统用于恶性疟原虫的大规模转座子诱变，以提高我们对疟原虫生物学遗传基础的理解，并大大加快开发新疗法的努力。

DESCRIPTION (provided by applicant): Malaria is a leading cause of human death and illness, causing each year 400-600 million cases of clinical malaria and 2-3 million deaths. Traditional measures to control and cure malaria are becoming increasingly ineffective, and there is an urgent need for the development of new drugs and vaccines. Genomic studies and other hi-tech advances have produced a wealth of information about malaria parasites; yet using this information for functional analysis of the Plasmodium genome is hindered by a limited capability to genetically manipulate malaria parasites. We are developing technology for high throughput whole-genome mutagenesis screening of malaria parasites, using an efficient transposon-based method for parasite transformation. We propose developing this system for large-scale transposon mutagenesis of Plasmodium falciparum with the long-term goal of enhancing our understanding of the genetic basis of the biology of the malaria parasite, and greatly accelerating efforts to develop new therapies.