Discovering the essential genome of Plasmodium falciparum

发现恶性疟原虫的基本基因组

基本信息

批准号：
10164710
负责人：
John H Adams
金额：
$ 64.37万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10164710
关键词：
African Anti-malarial drug resistance Antimalarials Artemisinins Blood Cambodia Cessation of life Clinical Clustered Regularly Interspaced Short Palindromic Repeats Collection Communities Culicidae Development Disease Drug Targeting Essential Drugs Essential Genes Exposure to Falciparum Malaria Fever Genes Genetic Genetic Screening Genotype Goals Growth Growth and Development function Heat-Shock Response Human In Vitro Infection Knowledge Libraries Link Malaria Measures Metabolic Pathway Methods Mutagenesis Open Reading Frames Oxidative Stress Parasites Parents Pathway interactions Phase Phenotype Physiology Plasmodium falciparum Plasmodium falciparum genome Plasmodium genome Process Recovery Recurrence Research Research Project Grants Resistance Site Stress Temperature Therapeutic Vaccines asexual base density drug discovery functional genomics gene complementation genome annotation genome-wide global health improved in vivo innovation knockout gene mutant next generation sequencing novel novel therapeutics novel vaccines reference genome response screening therapeutic target tool transcriptome sequencing transmission process vaccine discovery whole genome

项目摘要

Project Summary/Abstract Malaria is a leading cause of human death and illness, causing over 200 million cases of clinical malaria and 400,000 deaths each year. Traditional measures to control and cure malaria are becoming increasingly less effective and there is an urgent need for the development of new drugs and vaccines. A strategic hurdle for development of new anti-malarial therapeutics remains the lack of experimentally validated functional information about most Plasmodium falciparum genes. This is a critical gap of knowledge hindering identification of new drugs and vaccines. Therefore, efficient development of these new therapies requires a better understanding of essential metabolic pathways and weaknesses in the parasite’s physiology to target. Our approach is to use functional genomics studies to identify essential genes of P. falciparum through whole genome saturation-level piggyBac mutagenesis and forward genetic screens. Preliminary studies have validated this approach to identify essential and dispensable processes for asexual blood-stage growth under ideal in vitro culture conditions. We will extend these studies to identify factors essential for in vivo survival, too. Through this project, we expect to identify most genes critical for parasite blood-stage growth and development helping to identify and prioritize novel targets on which drug and vaccine discovery projects can be initiated. In addition, this project will provide the malaria research community with a large collection of gene knockouts valuable for many other research projects.

项目概要/摘要疟疾是人类死亡和疾病的主要原因，导致超过 2 亿例临床疟疾病例每年有 40 万人死亡，控制和治疗疟疾的传统措施正日益变得越来越重要。效果较差，迫切需要开发新药和疫苗。开发新的抗疟疾疗法的障碍仍然是缺乏经过实验验证的大多数恶性疟原虫基因的功能信息这是一个关键的知识空白。因此，阻碍了新药物和疫苗的有效开发。需要更好地了解寄生虫的基本代谢途径和弱点我们的方法是利用功能基因组学研究来识别 P. 恶性疟原虫通过全基因组饱和水平的piggyBac诱变和正向遗传筛选。初步研究已经验证了这种方法，以确定必要和可有可无的流程我们将扩展这些研究以确定理想的体外培养条件下的无性血液阶段生长。对于体内生存也至关重要的因素通过这个项目，我们希望识别出大多数对体内生存至关重要的基因。寄生虫血液阶段的生长和发育有助于确定药物的新靶点并确定其优先顺序此外，该项目还将提供疟疾研究。社区拥有大量对许多其他研究项目有价值的基因敲除数据。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Targeting Gametocytes of the Malaria Parasite Plasmodium falciparum in a Functional Genomics Era: Next Steps.

DOI：
10.3390/pathogens10030346
发表时间：
2021-03-16
期刊：
Pathogens (Basel, Switzerland)
影响因子：
0
作者：
Chawla J;Oberstaller J;Adams JH
通讯作者：
Adams JH

The apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite.

DOI：
10.1038/s41467-021-24814-1
发表时间：
2021-07-27
期刊：
Nature communications
影响因子：
16.6
作者：
Zhang M;Wang C;Oberstaller J;Thomas P;Otto TD;Casandra D;Boyapalle S;Adapa SR;Xu S;Button-Simons K;Mayho M;Rayner JC;Ferdig MT;Jiang RHY;Adams JH
通讯作者：
Adams JH

Protein KIC5 is a novel regulator of artemisinin stress response in the malaria parasite Plasmodium falciparum.

DOI：
10.1038/s41598-023-27417-6
发表时间：
2023-01-09
期刊：
Scientific reports
影响因子：
4.6
作者：
通讯作者：

Artemisinin resistance phenotypes and K13 inheritance in a Plasmodium falciparum cross and Aotus model.

恶性疟原虫杂交和 Aotus 模型中的青蒿素耐药表型和 K13 遗传。

DOI：
10.1073/pnas.1813386115
发表时间：
2018
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Sá,JulianaM;Kaslow,SarahR;Krause,MichaelA;Melendez-Muniz,VivianaA;Salzman,RebeccaE;Kite,WhitneyA;Zhang,Min;MoraesBarros,RobertoR;Mu,Jianbing;Han,PaulK;Mershon,JPatrick;Figan,ChristineE;Caleon,RamoncitoL;Rahman,Rifat
通讯作者：
Rahman,Rifat

Essential Genes of the Parasitic Apicomplexa.