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

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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.