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Title: Female sterile (1) homeotic controls metabolic and immune function and enhances survival via AKT and FOXO
Author: Sharrock, Jessica
ISNI:       0000 0004 6497 9940
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2017
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The Drosophila melanogaster fat body, analogous to mammalian adipose tissue and the liver, is the primary organ of fat and glycogen storage as well as being responsible for the humoral immune response following infection. Normal functioning of the fat body is of critical importance to the survival of the organism, but many molecular regulators of its function remain ill-defined. Here, for the first time, we demonstrate that the Drosophila bromodomain-containing protein fs(1)h is essential in the fat body for normal lifespan as well as metabolic and immune homeostasis. Under physiological conditions, flies lacking fs(1)h in the fat body exhibit a severely reduced lifespan, abnormally high expression of immune target genes including antimicrobial peptides (AMPs) and cytokines, an inability to utilise triglycerides following periods of starvation, and low basal AKT activity, mostly resulting from systemic defects in insulin signalling. Loss of fs(1)h in the fat body also results in hypoglycemia and a dysregulation of several fat body-derived signals, indicating a role for fat body fs(1)h in the regulation of various systemic endocrine signals. Removing a single copy of the AKT-responsive transcription factor foxo ameliorates almost all the observed phenotypes, restoring lifespan, metabolic function, uninduced immune gene expression, and AKT activity suggesting many of the in vivo effects of fs(1)h in the fat body are foxo-dependent. However, survival is not rescued and AMP expression is still elevated following bacterial infection in fs(1)h knockdown foxo heterozygous flies, indicating some of the phenotypes observed are independent of the FOXO hyperactivation. We propose that the promotion of systemic insulin signalling activity is a key in vivo function of fat body fs(1)h.
Supervisor: Taams, Leonie Suzanne ; Dionne, Marc Stuart Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available