ROLE OF PFHO-1 IN P. FALCIPARUM INTRAERYTHROCYTIC DEVELOPMENT
PFHO-1 在恶性疟原虫红细胞内发育中的作用
基本信息
- 批准号:8662416
- 负责人:
- 金额:$ 17.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-02-06 至 2016-01-31
- 项目状态:已结题
- 来源:
- 关键词:Aminolevulinic AcidAntimalarialsBindingCell NucleusCellsChIP-seqChloroquineCountryDNADNA BindingDevelopmentDiseaseDominant-Negative MutationErythrocytesEscherichia coliFoodGene DeletionGene ExpressionGene TargetingGenesGenetic EngineeringGoalsGrowth and Development functionHemeHemoglobinHemopexinHomeostasisHumanKnock-outKnowledgeMalariaOrganismOxygenasesParasitesPeptide HydrolasesPeptidesPhenotypePlasmodium falciparumPlayPorphyrinsProductionProtease InhibitorProtein BindingProtein BiosynthesisProteinsReporterRibosomal RNARoleSignal TransductionSourceSupplementationSystemTestingTimeTransfer RNAVacuoleViralchemotherapyheme aheme biosynthesisinfancyknockout genemutantnew technologyporphyrin aprotoporphyrin IXpublic health relevanceresearch studyresponse
项目摘要
Abstract
Exploration of the control of Plasmodium falciparum intraerythrocytic growth and
development is in its infancy. Understanding the signals and effectors of parasite
progression will enhance our knowledge of how this parasite survives in its host
cell and will uncover new targets for chemotherapy. PfHO-1 is a heme
oxygenase-like protein of unknown function expressed in intraerythrocytic
malaria parasites. We have found that PfHO-1 has a porphyrin-responsive DNA-
binding activity and associates preferentially with genes that are involved in
protein synthesis. Our hypothesis is that PfHO-1 responds to heme accumulation
from hemoglobin degradation and is crucial for intra-erythrocytic P. falciparum
development. The goal of the study proposed here is to test this hypothesis. We
will assess the response of PfHO-1 to perturbation of intracellular porphyrin
levels in intraerythrocytic P. falciparum and in an E. coli reporter system. We will
impair PfHO-1 action by a new double-positive selection gene knockout
approach and by conditional expression of a porphyrin-unresponsive version of
the protein. These studies will allow us to establish whether PfHO-1 plays an
important role in sensing cellular porphyrin levels and participating in critical
aspects of cellular homeostasis. The proposed experiments will also develop
new technologies for porphyrin manipulation and for selection of deleterious
phenotypes in reverse genetically engineered parasites.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Daniel E. Goldberg其他文献
Characterization of Membrane Contact Sites for the Facilitation of Lipid Exchange at the Malaria Parasite - Red Blood Cell Interface
- DOI:
10.1016/j.bpj.2019.11.3119 - 发表时间:
2020-02-07 - 期刊:
- 影响因子:
- 作者:
Matthias Garten;Josh Beck;Robyn Roth;John E. Heuser;Tatyana Tenkova-Heuser;Christopher K.E. Bleck;Daniel E. Goldberg;Joshua Zimmerberg - 通讯作者:
Joshua Zimmerberg
The structure of Ascaris hemoglobin domain I at 2.2 A resolution: molecular features of oxygen avidity.
2.2 A 分辨率下蛔虫血红蛋白结构域 I 的结构:氧亲合力的分子特征。
- DOI:
- 发表时间:
1995 - 期刊:
- 影响因子:11.1
- 作者:
Jian Yang;A. P. Kloek;Daniel E. Goldberg;F. Mathews - 通讯作者:
F. Mathews
When the Host Is Smarter Than the Parasite
当宿主比寄生虫更聪明时
- DOI:
- 发表时间:
2002 - 期刊:
- 影响因子:56.9
- 作者:
Daniel E. Goldberg - 通讯作者:
Daniel E. Goldberg
Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis
疟疾寄生虫需要不同的血红素加氧酶来进行顶质体基因表达和生物合成
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Amanda Mixon Blackwell;Y. Jami;Armiyaw S. Nasamu;S. Kudo;A. Senoo;Celine Slam;Kouhei Tsumoto;James A. Wohlschlegel;J. Caaveiro;Daniel E. Goldberg;P. Sigala - 通讯作者:
P. Sigala
ColE1 hybrid plasmids for Escherichia coli genes of glycolysis and the hexose monophosphate shunt
用于大肠杆菌糖酵解和己糖单磷酸分流基因的 ColE1 杂交质粒
- DOI:
10.1128/jb.137.1.502-506.1979 - 发表时间:
1979 - 期刊:
- 影响因子:3.2
- 作者:
Jennifer Thomson;T. P. D. Gerstenberger;Daniel E. Goldberg;Eva Gociar;Arminda Orozco DE Silva;D. Fraenkel - 通讯作者:
D. Fraenkel
Daniel E. Goldberg的其他文献
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{{ truncateString('Daniel E. Goldberg', 18)}}的其他基金
Specificity of Plasmodium falciparum protein export
恶性疟原虫蛋白输出的特异性
- 批准号:
10632093 - 财政年份:2022
- 资助金额:
$ 17.94万 - 项目类别:
Defining the resistome in P. falciparum: evolution and mechanism
恶性疟原虫抗性组的定义:进化和机制
- 批准号:
10608899 - 财政年份:2022
- 资助金额:
$ 17.94万 - 项目类别:
Specificity of Plasmodium falciparum protein export
恶性疟原虫蛋白输出的特异性
- 批准号:
10508060 - 财政年份:2022
- 资助金额:
$ 17.94万 - 项目类别:
Structural Vaccinology and Design of Novel Imunogens for Malaria Vaccine Development
用于疟疾疫苗开发的结构疫苗学和新型免疫原设计
- 批准号:
10330551 - 财政年份:2018
- 资助金额:
$ 17.94万 - 项目类别:
Plasmepsin X function in Plasmodium
Plasmodium 中 Plasmepsin X 的功能
- 批准号:
10322714 - 财政年份:2018
- 资助金额:
$ 17.94万 - 项目类别:
IDENTIFICATION OF THE ANTIMALARIAL TARGET OF PEPSTATIN ESTERS
胃酶抑素酯抗疟靶点的鉴定
- 批准号:
8734676 - 财政年份:2014
- 资助金额:
$ 17.94万 - 项目类别:
ROLE OF PFHO-1 IN P. FALCIPARUM INTRAERYTHROCYTIC DEVELOPMENT
PFHO-1 在恶性疟原虫红细胞内发育中的作用
- 批准号:
8802857 - 财政年份:2014
- 资助金额:
$ 17.94万 - 项目类别:
IDENTIFICATION OF THE ANTIMALARIAL TARGET OF PEPSTATIN ESTERS
胃酶抑素酯抗疟靶点的鉴定
- 批准号:
8852545 - 财政年份:2014
- 资助金额:
$ 17.94万 - 项目类别:
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