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Mass Spectrometry and Genetic Analysis of Biological Barrier Lipids

Newell, Clare Laura Louise; (2021) Mass Spectrometry and Genetic Analysis of Biological Barrier Lipids. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Malnutrition during embryonic development can have significant health ramifications for the adult organism. Such developmental programming effects have been studied in a variety of different organs but no research to date has looked at the largest organ in the body, the skin. One important and evolutionarily conserved role of the skin is to provide a lipid barrier against stresses in the external environment. Here, I utilise the short lifespan and powerful genetics of Drosophila melanogaster to investigate how cuticular barrier lipids are regulated by developmental diet and environmental stresses in the adult. The Drosophila cuticle is significantly different from the mammalian skin, yet both are coated with a waterproof lipid blend synthesised by specialised subepidermal cells - sebocytes in mammals and oenocytes in Drosophila. Research on the composition and regulation of lipid barriers has been hampered, at least in part, by the lack of methods for resolving surface lipids from intracellular lipids. I therefore optimise several techniques for analysing surface lipids, including a new cryogenic platform for mass spectrometry imaging. I demonstrate that developmental diet programmes the blend of adult cuticular lipids in both Drosophila and mice by increasing the adult skin wax esters. In Drosophila, I also show how adult environmental stresses impact upon the cuticle lipid blend. Combining mass spectrometry imaging with genetic analysis in Drosophila, I then identify a physiological feedback circuit that regulates the blend of adult cuticular hydrocarbons in response to increased housing density. This circuit involves the detection of housing density by an as yet unknown mechanism, information relay to oenocytes, and export of hydrocarbons to the cuticle surface via Obp99b/Obp99d odorant-binding proteins. Finally, I discuss the wider implications of this study and how mammals may regulate their skin lipids in line with a changing environment.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Mass Spectrometry and Genetic Analysis of Biological Barrier Lipids
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10131799
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