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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.

项目总结/摘要疟疾是人类死亡和疾病的主要原因，造成2亿多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越来越多，因此，迫切需要开发新的药物和疫苗。战略开发新的抗疟疾治疗方法的障碍仍然是缺乏实验验证，关于大多数恶性疟原虫基因的功能信息。这是一个关键的知识缺口阻碍了新药和疫苗的鉴定。因此，这些新疗法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，生理目标。我们的方法是利用功能基因组学的研究，以确定关键基因的P。通过全基因组饱和水平piggyBac诱变和正向遗传筛选，初步研究已经验证了这种方法，以确定必要的和可持续的过程，在理想的离体培养条件下无性血阶段生长。我们将扩展这些研究，也是体内存活所必需的因素。通过这个项目，我们希望能够确定大多数基因的关键，寄生虫血液阶段的生长和发育，有助于确定和优先考虑新的目标，疫苗研发项目可以启动。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。

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：

Essential Genes of the Parasitic Apicomplexa.

DOI：
10.1016/j.pt.2020.11.007
发表时间：
2021-04
期刊：
Trends in parasitology
影响因子：
9.6
作者：
Oberstaller J;Otto TD;Rayner JC;Adams JH
通讯作者：
Adams JH

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