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Mechanisms of RNA regulation in the persistence of the AIDS pathogen Toxoplasma

艾滋病病原体弓形虫持续存在的RNA调控机制

基本信息

批准号：
8848229
负责人：
LAURA J KNOLL
金额：
$ 18.7万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
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：
2014-11-01 至 2016-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8848229
关键词：
3&apos Untranslated Regions Acquired Immunodeficiency Syndrome Acute Address Animal Model Animals Binding Biochemistry Biological Brain Cellular biology Chelating Agents Chronic Cyst DNA-Binding Proteins Data Data Set Development Disease Drug Targeting Encephalitis Ensure Epitopes Felis catus Foundations Funding Future Gene Expression Profile Genes Goals Human Immunocompromised Host Immunologic Surveillance Immunoprecipitation Infection Ingestion Intervention Knowledge Maintenance Meat Messenger RNA Methods Modeling Molecular Molecular Analysis Mus Oocysts Parasites Patients Persons Pharmaceutical Preparations Pharmacologic Substance Poly A Poly C Poly G Poly U Process Protein Binding Proteins RNA RNA Binding Reading Reagent Refractory Regulation Resolution Role Staging Testing Therapeutic Time Tissue-Specific Gene Expression Tissues Toxoplasma Toxoplasma gondii Toxoplasmosis Transcript Trypanosoma brucei brucei Tubulin Vaccines Work Zinc Zinc Fingers base biological systems drug development effective therapy foodborne high risk homologous recombination in vivo mutant next generation sequencing novel overexpression pathogen prevent promoter public health relevance research study stem tissue culture transcriptome sequencing undercooked web site

项目摘要

DESCRIPTION (provided by applicant): Toxoplasma gondii can cause fatal infections in persons who are immunocompromised by AIDS. Patients with AIDS are especially vulnerable because there is no effective therapy against an established chronic infection of T. gondii. The paucity of effective therapeutics against T. gondii chronic infection in AIDS patients stems largely from the fact that few in vivo cyst drug targets have been identified. Our primary goal in studying T. gondii is to understand the molecular basis by which it causes disease to identify proteins that can be targeted to prevent T. gondii cyst development and/or maintenance. Using next generation sequencing methods, we have identified novel mechanisms of post-transcriptional RNA regulation during T. gondii chronic infection. We have seen that two of the 37 T. gondii CCCH zinc finger genes are more than 100- fold upregulated from acute to chronic infection. CCCH zinc finger proteins bind to and regulate mRNA abundance, and have been shown to control stage-specific development in the protozoan parasite Trypanosoma brucei. For this proposal, we will perform a mechanistic analysis of these two chronic infection-specific CCCH zinc finger proteins during chronic infection establishment and/or maintenance. In the first aim, we will determine the intracellular localization of these proteins as well as their RNA, DNA and protein-binding partners. In the second aim, we will use RNA-seq to define the potential mRNAs that these CCCH zinc finger proteins regulate. Successful completion of our synergistic yet independent aims will produce both potential mechanisms and new candidate target mRNAs for these zinc finger proteins. We are optimistic that these studies will provide new drug targets for pharmaceutical intervention against chronic T. gondii infections in AIDS patients.