Understanding the Regulation of Innate Immune Mechanisms and Its Relevance in Diseases Using Drosophila Melanogaster
Date of Award
Doctor of Philosophy (PhD)
School of Biological Sciences
Nathan T. Mortimer
Drosophila melanogaster is an excellent model organism to study conserved innate immune mechanisms. D. melanogaster utilizes both humoral and cellular immune responses to combat fungal, bacterial and parasitic pathogens; The cellular immune response targets parasites and parasitoid wasps are a major parasite of D. melanogaster. Fly larvae are commonly infected by parasitoid wasps and in response, mount a robust cellular immune response against the parasitoid egg. Numerous signaling pathways like JNK and JAK-STAT have been shown to play a role in the immune response against parasitoid wasps and have a conserved role in human immunity. However, the regulation of the conserved signaling pathways controlling innate immunity is not completely understood. Work done in Chapter I aims to better understand the role of CR44125, a long non-coding RNA as a novel regulator of Drosophila cellular immune response. Our findings suggest that CR44125 is involved in immune cell differentiation process by regulating the activity of the Jun N-terminal kinase (JNK) signaling pathway. Cellular immune mechanisms have evolved to coordinate various responses and maintain a balanced immune outcome. This involves the immune cells to maintain self-tolerance and exert immune response in a timely and regulated manner. Innate immune mediated self-tolerance mechanisms and the underlying genetic basis associated with the maintenance of this system remain largely unexplored and work done in Chapter II can provide insight into the transcriptional and physiological changes underlying self-tolerance and autoimmunity. Our findings suggest that Rel/NFκB transcriptional activity is associated with pro-inflammatory signaling in Drosophila, during loss of self-tolerance reactions. Thus, in general although immune cells via various innate immune mechanisms recognize cues from external pathogens to recognizing altered self like aberrant tissues or cancer cells, the functional role of the immune system and its underlying mechanisms in regulating tumorigenesis are poorly investigated. Our study in Chapter III utilizes the established Drosophila melanogaster model of tumor pathogenesis was used to study the impacts of innate immune response on tumor progression and metastasis. Recent studies have also shown that infections can also modulate tumorigenesis and thus, we use Drosophila-parasitoid as a host-parasite system to particularly dissect the role of infection in cancer pathogenesis. Our findings identified that G1Fl infection reduces both primary and secondary tumor growth and the model can further be used to characterize the mechanism by which an infection modifies tumorigenesis.
Kadaba Ranganath, Pooja, "Understanding the Regulation of Innate Immune Mechanisms and Its Relevance in Diseases Using Drosophila Melanogaster" (2022). Theses and Dissertations. 1531.
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