{"652917":{"#nid":"652917","#data":{"type":"event","title":"PhD Defense by Anuj Gupta","body":[{"value":"\u003Cp\u003EIn partial fulfillment of the requirements for the degree of\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDoctor of Philosophy in Bioinformatics\u003C\/p\u003E\r\n\r\n\u003Cp\u003Ein the School of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EAnuj Gupta\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDefends his thesis:\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EComputational investigation of the molecular basis of susceptibility and resilience in different macaque species infected with malaria causing \u003Cem\u003EPlasmodium\u003C\/em\u003E pathogens\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003ETuesday, November 30, 2021\u003C\/p\u003E\r\n\r\n\u003Cp\u003E11:15am Eastern Time\u003C\/p\u003E\r\n\r\n\u003Cp\u003EBlueJeans link:\u0026nbsp;\u003Ca href=\u0022https:\/\/bluejeans.com\/375899958\/4887\u0022\u003Ehttps:\/\/bluejeans.com\/375899958\/4887\u003C\/a\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EThesis Advisor:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. Eberhard O. Voit\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDepartment of Biomedical Engineering\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ECommittee Members:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. I. King Jordan\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. Mark P. Styczynski\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Chemical and Biomolecular Engineering\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. Peng Qiu\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDepartment of Biomedical Engineering\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. Mary R. Galinski\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Medicine\u003C\/p\u003E\r\n\r\n\u003Cp\u003EEmory University\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ESummary:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EMalaria has a complex pathology with varying manifestations and symptoms, effects on host tissues, and different degrees of severity and ultimate outcome, depending on the causative \u003Cem\u003EPlasmodium \u003C\/em\u003Epathogen species. The studies in this dissertation analyze consequences of transcriptomic changes in the blood of two closely related macaque species (\u003Cem\u003EMacaca mulatta\u003C\/em\u003E and \u003Cem\u003EMacaca fascicularis\u003C\/em\u003E) in response to acute primary infection by \u003Cem\u003EPlasmodium knowlesi\u003C\/em\u003E. \u003Cem\u003EP. knowlesi\u003C\/em\u003E is an emanant zoonotic pathogen that causes acute severe infection in humans. Although the two macaque species are very closely related to each other and to humans, the infection in \u003Cem\u003EM. mulatta\u003C\/em\u003E is fatal, unless aggressively treated (similar to humans), whereas \u003Cem\u003EM. fascicularis\u003C\/em\u003E develops a chronic, but tolerable infection.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe comparative analysis described here suggests that a reason for this stark difference in outcome is that the two hosts differ in immune cell programs and expression of important genes. Specifically, the analyses establish a delayed pathogen detection in \u003Cem\u003EM. mulatta\u003C\/em\u003E followed by extended inflammation that overwhelms this monkey\u0026rsquo;s immune response. By contrast, \u003Cem\u003EM. fascicularis\u003C\/em\u003E was found to detect the pathogen earlier and to control the inflammation. Additionally, \u003Cem\u003EM. fascicularis\u003C\/em\u003E limits cell proliferation pathways until peak infection, presumably in an attempt to reinforce recovery through the adaptive immune system. To compliment this transcriptomics analysis, a gene expression aided metabolic modeling approach was developed that combined multi-omics knowledge to give a molecular interpretation to biological systems. This helped to interpret changes in inflammation biomarker, Kyn\/Trp ratio, and relate it to differences in immune response and cell proliferation. In depth analysis of observed differences reveals that pattern-recognition receptor (PRR) signaling pathways are crucial for detection of pathogen and transcriptomic differences in early liver phase of infection revealed an early detection in \u003Cem\u003EM. fascicularis\u003C\/em\u003E. Correlation analysis between host and pathogen transcripts reveals a pathogenic surface antigen, SICAvar Type 1, as an important regulator throughout the infection. The log phase of infection in hosts is similar with macrophages and monocytes responsible for innate immune responses. During this phase, \u003Cem\u003EM. mulatta\u003C\/em\u003E shows higher inflammation signals with upregulated inflammasome IL6-JAK-STAT3 signaling and IL10 expression, which continues to peak-infection phase. In contrast,\u003Cem\u003E M. fascicularis\u003C\/em\u003E controls inflammation, presumably by means of the p53 pathway, which is distinctly downregulated near the peak of infection, thereby enabling adaptive immunity with various cell proliferation pathways that aid CD4+ T-cells and memory B-cells. Integrative metabolic modeling shows the potential role of tryptophan metabolism in regulating inflammation and stress response. \u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EA complete understanding of the exact dynamics of the immune response is difficult to reach. Nonetheless, studies in this dissertation provide clear indication toward processes that underlie an effective immune response. Thus, this study may pave the way for future immune strategies toward treating malaria and identifies multiple points of intervention that are apparently responsible for a balanced and effective immune response.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"Computational investigation of the molecular basis of susceptibility and resilience in different macaque species infected with malaria causing Plasmodium pathogens"}],"uid":"27707","created_gmt":"2021-11-16 18:56:29","changed_gmt":"2021-11-16 18:56:29","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2021-11-30T11:15:00-05:00","event_time_end":"2021-11-30T13:30:00-05:00","event_time_end_last":"2021-11-30T13:30:00-05:00","gmt_time_start":"2021-11-30 16:15:00","gmt_time_end":"2021-11-30 18:30:00","gmt_time_end_last":"2021-11-30 18:30:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"groups":[{"id":"221981","name":"Graduate Studies"}],"categories":[],"keywords":[{"id":"100811","name":"Phd Defense"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1788","name":"Other\/Miscellaneous"}],"invited_audience":[{"id":"78761","name":"Faculty\/Staff"},{"id":"78771","name":"Public"},{"id":"78751","name":"Undergraduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}