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Innate immune regulation and aging in Drosophila melanogaster

Posted on:2008-03-09Degree:M.ScType:Thesis
University:Queen's University (Canada)Candidate:Hennessy, Robert RFull Text:PDF
GTID:2444390005466926Subject:Biology
Abstract/Summary:
Aging is associated with an up-regulation of innate immune components in many model organisms. It is unknown if this increased transcriptional activity contributes to the aging process, or is simply a consequence of it. Herein this question is examined through utilization of the UAS/GAL4 and GeneSwitch systems to over-express immune components, in a tissue specific manner, in developing and young adult Drosophila melanogaster, respectively.;The problem of molecule-specific toxicity could be avoided through the mutation of genes that repress the flies' immune system. PGRP-LF is believed to be such a repressor. Eight potential PGRP-LF mutants had been previously generated through the imprecise excision of a P-element from the DJ646 strain, where it is inserted adjacent to the PGRP-LF coding region. These potential mutants were examined through complementation, PCR, and sequencing experiments. Results are inconclusive for most lines but one, Delta12, has a deletion of approximately 1300bp in what could be part of the PGRP-LF regulatory region. Complementation experiments suggest that, with the exception of line 20, all Delta strains have mutations in the same gene. Thus, it is likely that the other lines also have a mutation in their PGRP-LF gene. It appears unlikely that up-regulation of innate immune components at midlife contributes to aging. This, along with the consistency of the up-regulation, suggests that immune components may be useful as easily discernable biomarkers. A reliable biomarker of aging could revolutionize aging research by making work with model organisms less resource intensive and work with humans feasible.;Analysis revealed that the expression of many immune components could hinder survival during development, particularly when localized in muscle tissue. Over-expression of non-endpoint components of the immune pathways, such as receptors and signal transduction molecules, resulted in increased mortality rates vs. over-expression of antimicrobial peptides. Molecules from the imd pathway that hindered development the most were selected for longevity experiments. These experiments suggest that the pattern precognition receptor PGRP-LCx may have a toxic effect if expressed in the adipose tissues of the thorax and abdomen but over-expression of immune components, in general, likely has no affect on longevity.
Keywords/Search Tags:Immune, Aging, PGRP-LF
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