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 贫血在世界范围内导致重大疾病，并不成比例地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，受宿主生理的影响，包括血液代谢物水平和肠道 微生物区系组成。虽然肠道微生物已知会影响造血，但有关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，因此这是一种 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病或恢复有关的生物因素。目标是 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有关 发生在疟疾贫血期间。这项研究项目的中心目标是：1)确定 血液代谢物和肠道微生物在疟疾贫血发生中的作用和2)决定程度 细菌易位和菌血症与疟疾的血液学变化有关。两者都有 AIMS将包括对感染了猪流感病毒的非人灵长类动物的纵向感染研究的样本进行分析 疟疾寄生虫疟原虫。高通量生物技术，如代谢组学和 元基因组学，数据集成和网络分析等计算方法，以及详细的 组织上的免疫荧光研究将全部用于寄主和共生体的多组学分析 疟疾贫血背景下的微生物因素。申请者Regina Joice Cordy博士是一名初级教员 埃默里大学会员，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专业公司的物流经验。 制度系统生物学项目。在她现有技能的基础上，添加新的补充技能 元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 目的是识别特定的血液代谢物和/或肠道微生物，这些代谢产物和/或肠道微生物与 从疟疾贫血中恢复，朝着确定预后生物标志物和代谢或益生菌的目标 毒品目标。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 使用埃默里最先进的基础设施进行纵向多组体系统生物学 对非人类灵长类动物的研究。此外，科迪博士还组建了一支由导师、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科迪博士 启动了一项长期研究计划，重点是调查贫血的系统生物学。