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.

项目摘要/摘要 贫血在世界范围内引起重大疾病，并对非洲人和非裔美国人产生不成比例的影响。 贫血的主要原因包括营养缺乏症，血红蛋白病和寄生疟疾。 疟疾贫血是多因素的，受宿主生理的影响，包括血液代谢物水平和肠道 微生物群的组成。虽然已知肠道微生物会影响造血，但关于 肠道微生物在不同类型贫血的发育或恢复中的作用，因此这是一个 值得调查领域。系统生物学提供了破译复杂过程和 在计算上识别与贫血发作或恢复相关的生物学因素。目标 这项研究的是确定血液代谢物和肠道微生物与血液学变化的联系 这在疟疾贫血期间发生。该研究项目的主要目的是1）确定关联 血液代谢产物和肠道微生物在疟疾贫血的发展中，2）确定程度 细菌易位和细菌与疟疾血液学变化有关。两个都 目的将涉及分析来自感染的非人类灵长类动物的纵向感染研究 疟原虫疟原虫。高通量`代谢组学等高通量技术 宏基因组学，数据集成和网络分析等计算方法以及详细 关于组织的免疫荧光研究将全部用于宿主和共生的多摩尼 疟疾贫血的微生物因子。申请人里贾纳·乔斯·科迪（Regina Joice Cordy）博士是初级教师 埃默里大学（Emory University）的成员，具有寄生虫学，宿主病原体相互作用和 计算生物学。她还具有管理大型跨学科多跨学科的物流的经验 机构系统生物学计划。基于她目前的技能，并在 宏基因组学和网络分析，实验血液学和免疫荧光成像，科迪博士 旨在确定与发展或 从疟疾贫血恢复到识别预后生物标志物和代谢或益生菌的目标 药物靶标。埃默里大学的玛丽·R·加林斯基教授将担任主要导师，科迪博士将拥有 访问基于Emory的最先进的基础设施，用于执行纵向多摩变系统生物学 非人类灵长类动物的研究。此外，Cordy博士组建了一支多样化的导师，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 启动一项长期研究计划的重点是研究贫血的系统生物学。