Circadian regulation of innate immunity and microRNAs in Drosophila melanogaster:

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.Ph.D.Includes bibliographical references (p. 110-125)by Jung-Eun Le