A systems biology investigation of the interplay between gut microbes and blood metabolites in the development of malarial anemia

肠道微生物与血液代谢物在疟疾贫血发展过程中相互作用的系统生物学研究

• 批准号: 9767275
• 负责人: Regina J Cordy
• 金额: $ 14.67万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-20 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9767275
• 关键词: 16S ribosomal RNA sequencing; Acute; Affect; African American; Age; Anemia; Animals; Archives; Area; Bacteremia; Bacterial Translocation; Bacteroidetes; Biological Factors; Biological Models; Blood; Blood Circulation; Blood specimen; Bone Marrow; Child; Clinical; Complex; Complication; Computational Biology; Computer Analysis; Cytolysis; Data; Data Set; Databases; Development; Diagnosis; Diet; Disease; Drug Targeting; Epithelial; Erythrocytes; Exhibits; Experimental Hematology; Faculty; Falciparum Malaria; Functional disorder; Funding; Genes; Genetic; Goals; Hematology; Hematopoiesis; Hematopoietic; Hemoglobinopathies; Histopathology; Human; Image; Immunofluorescence Immunologic; Immunohistochemistry; Immunology; Individual; Infection; Information Systems; Infrastructure; Investigation; Lead; Link; Logistics; Macaca; Macaca mulatta; Malaria; Measures; Mediating; Mentors; Mentorship; Metabolic; Metabolic Pathway; Metabolism; Metagenomics; Microbe; Microbiology; Molecular; Morbidity - disease rate; Multi-Institutional Systems; Mus; National Institute of Allergy and Infectious Disease; Nutrient; Parasites; Parasitic Diseases; Parasitology; Pathway Analysis; Physiology; Plasmodium; Plasmodium falciparum; Play; Probiotics; Process; Prognostic Marker; Proteobacteria; Recovery; Research; Research Project Grants; Role; Sampling; Sampling Studies; Sepsis; Severities; Shotguns; Systems Biology; Tail; Taxonomy; Technology; Thrombocytopenia; Time; Tissues; Training; Universities; animal data; base; biomarker discovery; career; career development; clinically relevant; co-infection; cohort; data integration; experience; gene function; gut microbes; gut microbiome; gut microbiota; longitudinal dataset; malaria infection; malarial anemia; member; metabolomics; metagenomic sequencing; microbial; microbiome; microbiome analysis; molecular pathology; mortality; multiple omics; new therapeutic target; nonhuman primate; novel; pathogen; pathogenic bacteria; probiotic therapy; programs; research and development; skills

Project Summary/Abstract Anemia causes significant disease worldwide, and disproportionally affects Africans and African-Americans. Among the top causes of anemia are nutrient deficiency, hemoglobinopathy, and the parasitic disease malaria. Malarial anemia is multi-factorial and is affected by host physiology, including blood metabolite levels and gut microbiota composition. While gut microbes are known to affect hematopoiesis, there is very little data on the role of gut microbes in the development or recovery from different types of anemia, and this is therefore a worthwhile area of investigation. Systems biology offers the opportunity to decipher complex processes and computationally identify biological factors that are associated with the onset or recovery from anemia. The goal of this research is to determine how blood metabolites and gut microbes are linked to the hematological changes that occur during malarial anemia. The central aims of this research project are to 1) identify associations between blood metabolites and gut microbes in the development of malarial anemia and 2) determine the extent to which bacterial translocation and bacteremia are associated with hematological changes in malaria. Both aims will involve the analysis of samples from longitudinal infection studies of nonhuman primates infected with the malaria parasite Plasmodium. High-throughput `omic technologies such as metabolomics and metagenomics, computational approaches such as data integration and network analyses, and detailed immunofluorescence studies on tissue will all be used for the multi-omic profiling of host and commensal microbial factors in the context of malarial anemia. The applicant, Dr. Regina Joice Cordy, is a junior faculty member at Emory University and has a background in parasitology, host-pathogen interactions, and computational biology. She also has experience in managing the logistics of a large transdisciplinary multi- institutional systems biology program. Building upon her current skills, and adding new complementary skills in metagenomics and network analysis, experimental hematology, and immunofluorescence imaging, Dr. Cordy aims to identify specific blood metabolites and/or gut microbes that are associated with the development of, or recovery from malarial anemia, toward the goal of identifying prognostic biomarkers and metabolic or probiotic drug targets. Prof. Mary R. Galinski of Emory University will serve as the Primary Mentor and Dr. Cordy will have access to a state-of-the-art infrastructure based at Emory for performing longitudinal multi-omic systems biology studies in nonhuman primates. Further, Dr. Cordy has assembled a diverse team of mentors, collaborators and career advisors who will provide mentorship and advising for her research and career development objectives. The experience gained through the proposed training and research experience will prepare Dr. Cordy for initiating a long-term research program focused on investigating the systems biology of anemia.

项目总结/摘要 贫血在世界范围内引起重大疾病，并严重影响非洲人和非裔美国人。 贫血的主要原因是营养缺乏、血红蛋白病和寄生虫病疟疾。 疟疾贫血是多因素的，受宿主生理学影响，包括血液代谢物水平和肠道 微生物群组成。虽然已知肠道微生物会影响造血，但关于肠道微生物的数据很少。 肠道微生物在不同类型贫血的发展或恢复中的作用，因此这是一个 值得调查的领域。系统生物学提供了破译复杂过程和 通过计算确定与贫血发作或恢复相关的生物因素。目标 这项研究的目的是确定血液代谢物和肠道微生物如何与血液学变化联系起来 在疟疾性贫血时出现的症状本研究项目的主要目的是：1）识别 在疟疾贫血的发展中血液代谢物和肠道微生物之间的关系，以及2）确定 细菌移位和菌血症与疟疾的血液学变化有关。两 目的将涉及对非人灵长类动物感染的纵向感染研究样本的分析， 疟原虫代谢组学等高通量组学技术， 宏基因组学，计算方法，如数据集成和网络分析，以及详细的 对组织的免疫荧光研究将全部用于宿主和宿主的多组学分析。 微生物因素在疟疾贫血的背景下。申请人，里贾纳乔伊丝科迪博士，是一个初级教师 埃默里大学的成员，具有寄生虫学、宿主-病原体相互作用和 计算生物学她还拥有管理大型跨学科多学科物流的经验， 机构系统生物学计划。在她现有技能的基础上， 宏基因组学和网络分析，实验血液学和免疫荧光成像，Cordy博士 目的是确定与发展相关的特定血液代谢物和/或肠道微生物，或 从疟疾贫血中恢复，朝着鉴定预后生物标志物和代谢或益生菌的目标 药物靶点玛丽教授R.埃默里大学的Galinski将担任主要导师，Cordy博士将 进入埃默里大学最先进的基础设施，进行纵向多组学系统生物学研究 在非人类灵长类动物中的研究。此外，科迪博士还组建了一个由导师、合作者和 职业顾问将为她的研究和职业发展目标提供指导和建议。 通过拟议的培训和研究经验获得的经验将为Cordy博士做好准备 启动了一项长期研究计划，重点是调查贫血的系统生物学。