Thesis

Investigating the genetics of resistance to the mood stabiliser lithium

Creator
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Awarding institution
  • University of Strathclyde
Date of award
  • 2014
Thesis identifier
  • T13973
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Bipolar disorder affects approximately 1-2% of the world's population. The 'gold standard' medication to treat this disorder is the mood stabiliser lithium. Despite being in use for over 60 years, the mechanism of action of lithium is still not well understood, and only shows full efficacy in a third of patients. Understanding how lithium functions would aid our understanding of bipolar disorder and help design new treatments for the condition. This research project describes a method to identify and confirm genes involved in the lithium pathway. Gene identification is first performed by gene trapping, which identifies genes which are potentially involved in the pathway. Then confirmation of gene involvement was undertaken using the bacterial immune system CRISPR - a nuclease-based approach to downregulate a target gene. Before this could be achieved, the plasmid components of the CRISPR system had to be produced through genetic engineering. The solute carrier SLC25A40 was identified from the gene trapping stage. Additionally, a functional CRISPR system was successfully created and used to investigate a gene known to be involved in the lithium pathway - inositol monophospatase. A final experiment was undertaken to evaluate the brain and subcellular distribution of another gene, LPHN2, identified in a screen for genes resistant to a second mood stabiliser, valproate. My project has developed research tools that permit the molecular investigation of biological processes and pathways. Indeed, these tools are already being applied by others in the Institute to explore bacterial infection of mammalian cells. The studies on mood stabilisers indicate that genetic approaches can help better understand the actions of drugs and disease.
Resource Type
DOI
Date Created
  • 2014
Former identifier
  • 1217710

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file details File 2021-07-02 University of Strathclyde