Immunity, behavior, and circadian regulation are important ways that animals maintain homeostasis. Defects in these physiologies often lead to disease or even death, yet many questions remain about how these physiologies are related. I explored the interactions between innate immunity, behavior, and circadian regulation by using Drosophila melanogaster, a convenient, genetically tractable model organism with both functionally and molecularly conserved innate immune and circadian clock systems. In the first chapter, I show that feeding, a circadian-regulated behavior, increases immunity to a sepsis-like infection. In the second, I present evidence suggesting that aging-related changes in immunity may be linked to circadian defects. Finally, I use a novel automated method to demonstrate that reduced grooming is a conserved sickness behavior in Drosophila.
The feeding project ultimately showed that mutating TORC2 components could increase the host’s ability to kill and clear a bacterial infection, as well as survive the pathogenic effects of infection. Therefore we have identified a possible drug target to create host-based therapies for sepsis patients. We also have established Drosophila as a model system for studying a conserved sickness behavior: reduced grooming. This experimental paradigm will allow researchers to isolate mutants that do not show reduced grooming, and investigate whether this sickness behavior is adaptive or not.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/D89P31QP |
| Date | January 2016 |
| Creators | Allen, Victoria Wing |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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