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http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/2392 http://eprints.org/relation/ispreviewThumbnailVersionOf http://etheses.bham.ac.uk/id/document/2392 http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/2392 archive 4031 disk0/00/00/09/65 2010-09-30 13:55:12 2019-01-23 09:53:13 2011-07-19 16:26:50 thesis show 0 Gandhi Francis Amrit Raj May Robin C. University of Birmingham unpub QR 10col_life Ageing, immunity and stress tolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. In this project we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. We show, using phenotypic analysis of DAF-16 influenced phenotypes, that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (Caenorhabditis elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Quantitative Real-Time PCR, which positively correlate with the observed phenotypes. We also provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. Finally, we take a closer look at the daf-16 gene and its isoforms in C. elegans and their role in driving specific responses to stress. These findings impact upon our understanding of the diversification of the IIS pathway and the evolution of longevity in general, and illustrate how such differences could explain both inter and intra-species differences in ageing, immunity and stress response. 2010-07 graduation eng This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. public 201 University of Birmingham School of Biosciences d_ph na 2010-07 graduation