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Circadian regulation of innate immunity and microRNAs in Drosophila melanogaster
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Circadian regulation of innate immunity and microRNAs in Drosophila melanogaster
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ETD_1028
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000051762
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eng
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theses
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Biochemistry
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Circadian rhythms
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Drosophila melanogaster
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Immune response
Abstract
The main parts of my thesis are studies aimed at investigating circadian regulation of innate immunity using Drosophila as a model system. In unrelated work, I also participated in a collaborative study showing circadian regulation of microRNAs (miRNAs) in Drosophila.
We sought to determine if the innate immune response is under circadian regulation and whether this impacts overall health status. To this end, Drosophila was infected with the human opportunistic pathogenic bacteria Pseudomonas aeruginosa as a model system. The results show that the survival rates of wild-type flies vary as a function of when during the day they are infected, peaking in the middle of the night. Also the kinetics of bacterial growth and the expression of a limited number of innate immunity genes correlate with time-of-day effects on survival. Our findings suggest that medical intervention strategies incorporating chronobiological considerations could enhance the innate immune response, boosting the efficacy of combating pathogenic infections. This study also led us to a second study where we characterized the innate immune response in the Drosophila head. We showed that the innate immunity pathway in the head is similar to the well described pathway in the body. Furthermore, the pericerebral fat body in the head or neurons are sufficient to combat bacterial infections, independent of the abdominal fat body. Our findings suggest that the pericerebral fat body may provide a fast and local immune response in the head, improving the survival outcome of Drosophila.
A minor aspect of my thesis work was unrelated to host defense. In this study, we used Drosophila to investigate the possibility that circadian clocks regulate the expression of miRNAs. From the analysis of microarray data, we found two miRNAs (dme-miR-263a and -263b) that exhibit robust daily changes in abundance in adult heads of wild-type flies that are abolished in the cyc01 mutant. Our results suggest that cycling miRNAs contribute to daily changes in mRNA and/or protein levels in Drosophila.
We sought to determine if the innate immune response is under circadian regulation and whether this impacts overall health status. To this end, Drosophila was infected with the human opportunistic pathogenic bacteria Pseudomonas aeruginosa as a model system. The results show that the survival rates of wild-type flies vary as a function of when during the day they are infected, peaking in the middle of the night. Also the kinetics of bacterial growth and the expression of a limited number of innate immunity genes correlate with time-of-day effects on survival. Our findings suggest that medical intervention strategies incorporating chronobiological considerations could enhance the innate immune response, boosting the efficacy of combating pathogenic infections. This study also led us to a second study where we characterized the innate immune response in the Drosophila head. We showed that the innate immunity pathway in the head is similar to the well described pathway in the body. Furthermore, the pericerebral fat body in the head or neurons are sufficient to combat bacterial infections, independent of the abdominal fat body. Our findings suggest that the pericerebral fat body may provide a fast and local immune response in the head, improving the survival outcome of Drosophila.
A minor aspect of my thesis work was unrelated to host defense. In this study, we used Drosophila to investigate the possibility that circadian clocks regulate the expression of miRNAs. From the analysis of microarray data, we found two miRNAs (dme-miR-263a and -263b) that exhibit robust daily changes in abundance in adult heads of wild-type flies that are abolished in the cyc01 mutant. Our results suggest that cycling miRNAs contribute to daily changes in mRNA and/or protein levels in Drosophila.
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electronic resource
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xiii, 126 p. : ill.
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Ph.D.
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Includes bibliographical references (p. 110-125)
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by Jung-Eun Lee
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Lee
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Jung-Eun
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1969-
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Jung-Eun Lee
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Ruth Steward
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Edery
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Isaac
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Isaac Edery
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Williams
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Julie
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Julie A Williams
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Gelinas
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Celine
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Celine Gelinas
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Rutgers University
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Graduate School - New Brunswick
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2008
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2008-10
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xx
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Rutgers University Electronic Theses and Dissertations
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Graduate School - New Brunswick Electronic Theses and Dissertations
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doi:10.7282/T35D8S1S
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ETD doctoral
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Open
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Lee
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Jung-Eun
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Jung-Eun Lee
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Rutgers University. Graduate School - New Brunswick
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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