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Investigating the Role of Neuronal SKN-1 in C. elegans

Howard, Alexander Francis (2020) Investigating the Role of Neuronal SKN-1 in C. elegans. Master of Science by Research (MScRes) thesis, University of Kent,. (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:80065)

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Language: English

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Abstract

In C. elegans, the SKN-1/Nrf transcription factor is a crucial component for controlling responses to oxidative stress, redox balance, proteostasis, healthy ageing and improving lifespan. SKN-1 has three major isoforms that function independently of one another. SKN-1A and SKN-1C are localised in the C. elegans intestine and have been extensively studied. The third isoform, SKN-1B, is confined to two amphid chemosensory neurons in the head of C. elegans and is still relatively unexplored. Here, we investigate the role of SKN-1B in three major pathways that all contribute to longevity; the insulin/IGF-1 signalling (IIS) pathway, the endoplasmic reticulum unfolded protein response (UPRer) and mitochondrial morphology. Publications investigating the longevity effects of dietary restriction (DR) have also uncovered evidence that may suggest SKN-1B has a role here, and so therefore we also include conditional DR by two published methods; bacterial deprivation (BD) and liquid DR (lDR). We found that SKN-1B is not required for induction of DAF-16 nuclear localisation or expression upon DR, however nuclear localisation in SKN-1B mutant worms is short-lived compared to wildtype. Interestingly also, SKN-1B is required for increased expression of the DAF-16-target gene sod-3 using the lDR protocol, but not in BD. It was also discovered that SKN-1B positively regulates hsp-4 expression under non-stressed conditions, but it was not required for induction of hsp-4 expression during ER stress caused by ero-1 RNAi. In addition, the long-lived phenotype of ero-1 RNAi does not require SKN-1B and therefore its only role may be in basal expression of UPRer components under normal conditions. Finally, we found that SKN-1B mutant worms exhibit a mitochondrial morphology defect characterised by an increased network fragmentation that resembles a starved phenotype. SKN-1B mutant worms have a normal N2 lifespan, and so this phenotype is of an unknown physiological consequence. This data together provides new insights into the role of the under-studied SKN-1B transcription factor which can hopefully offer new directions for investigation. It has been shown that SKN-1B has multiple complex roles in many signalling pathways through neuroendocrine modulation; this along with its emerging role in behaviour present an exciting new area of research.

Item Type: Thesis (Master of Science by Research (MScRes))
Thesis advisor: Tullet, Jennifer
Uncontrolled keywords: C.elegans SKN1 Ageing Lifespan ASI IIS Insulin UPR Mitochondia DR Starvation
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Divisions: Faculties > Sciences > School of Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 14 Feb 2020 10:10 UTC
Last Modified: 17 Feb 2020 10:01 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/80065 (The current URI for this page, for reference purposes)
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