PRJNA524357
Malaria Host Pathogen Center Experiment 06: Macaca mulatta infected with Plasmodium knowlesi sporozoites to produce and integrate clinical, hematological, parasitological, omics, telemetric, and histopathological measures of acute primary infection. (GSE127079)
This project is part of the Malaria Host-Pathogen Interaction Center (MaHPIC) - a transdisciplinary malaria systems biology research program initially supported by an NIH/NIAID contract (# HHSN272201200031C, 2012-2017; see http://www.systemsbiology.emory.edu). The MaHPIC has continued with support from the Defense Advanced Research Project Agency (DARPA) and others. The MaHPIC generates many data types (e.g., clinical, hematological, parasitological, metabolomics, functional genomics, lipidomics, proteomics, immune response, telemetry) and mathematical models, to iteratively test and develop hypotheses related to the complex host-parasite dynamics in the course of malaria in non-human primates (NHPs), and metabolomics data via collaborations with investigators conducting clinical studies in malaria endemic countries, with the overarching goal of better understanding human disease, pathogenesis, and immunity. Curation and maintenance of all data and metadata are the responsibility of the MaHPIC. Overall design:  Telemetry devices (DSI, model L11) with blood pressure sensors and electrocardiogram (ECG) leads were surgically implanted in four malaria-naive male rhesus macaques (Macaca mulatta), approximately five years of age. After a resting period of two weeks, physiological data that include activity, temperature, ECG, and blood pressure were continuously collected. Two weeks after activation of the telemetry implant, the macaques were inoculated intravenously with cryopreserved P. knowlesi Malayan strain salivary gland sporozoites, obtained from Anopheles dirus infected with parasites from the Pk1A+ clone and previously tested in E30 for their infectivity of macaques. The sporozoite stocks used were produced, isolated and cryopreserved at the Centers for Disease Control and Prevention, and then stored at Yerkes. After inoculation, the macaques were profiled longitudinally for clinical, hematological, parasitological, immunological, functional genomic, proteomic, and metabolomic measurements. The experiment was designed with pathology studies and thus terminal necropsies, which were scheduled at the log phase of the infections or at the peak of parasitemias. Capillary blood samples were collected daily for the measurement of complete blood counts, reticulocytes, and parasitemias. Capillary blood samples were collected every other day to obtain plasma for metabolomics analyses. Venous blood and bone marrow samples were collected at five timepoints for functional genomic, targeted proteomic, targeted metabolomics, and immunological analyses. Physiological data noted above were continuously captured via the implanted telemetry devices. Within the MaHPIC, this project is known as 'Experiment 06'. This dataset was produced by Dr. Steven E. Bosinger, Nirav Patel, and Greg Tharp at the Emory University Yerkes Genomics Core. To access other publicly available results from E06 and other MaHPIC Experiments, including clinical results (specifics on drugs administered, diet, and veterinary interventions), and other omics, visit http://plasmodb.org/plasmo/mahpic.jsp. This page will be updated as datasets are released to the public. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC) and the MRMC Office of Research Protection Animal Care and Use Review Office (ACURO). The MaHPIC Consortium