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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

基本信息

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
项目类别：
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

项目摘要

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/文摘