Investigating lung function gene GSTCD using gene targeting in human and mouse systems

Probert, Kelly (2016) Investigating lung function gene GSTCD using gene targeting in human and mouse systems. MPhil thesis, University of Nottingham.

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Abstract

Respiratory diseases are a significant global health concern and burden, with one of the major respiratory diseases causing a decline in lung function being chronic obstructive pulmonary disease (COPD). Critically, current therapies have limited impact. Recently, single nucleotide polymorphisms at chromosome locus 4q24 have been identified as associated with the lung function measure forced expiratory volume in 1 second and COPD, specifically identifying the gene Glutathione S-transferase C-terminal domain containing (GSTCD) as a viable candidate gene. Data indicate that GSTCD or associated biological pathways may be a potential target for interventions to alleviate COPD. Further analysis into the pathways and phenotypic effects of this gene may aid our understanding of the mechanisms by which GSTCD is associated with and influences lung function and COPD.

Importantly, there are currently no reports describing the function of GSTCD, therefore this project aimed to understand the consequences of reduction and loss of GSTCD within the context of lung biology. This was performed by analysis of human cell knock-down and knock-out mouse models respectively, as well as utilising established protein sequence homology analysis to infer potential function.

Conclusions drawn from these results suggest a possible role for GSTCD in cell growth in a human in vitro GSTCD knock-down model, but no gross morphological differences were evident in Gstcd knock-out mice. Additionally, GSTCD sequence homology analysis in several protein prediction servers suggests methyltransferase activity as a potential function for GSTCD, differing from the initial prediction of glutathione S-transferase enzyme activity.

Overall, this research represents an important and novel development for the lung function and COPD associated gene GSTCD, providing interesting avenues for future exploration.

Item Type: Thesis (University of Nottingham only) (MPhil)
Supervisors: Hall, I.P.
Sayers, I.
Keywords: Glutathione S-transferase C-terminal domain, Chronic obstructive pulmonary disease, Lung function
Subjects: W Medicine and related subjects (NLM Classification) > WF Respiratory system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 33199
Depositing User: Probert, Kelly
Date Deposited: 22 Oct 2018 12:38
Last Modified: 08 Feb 2019 10:15
URI: http://eprints.nottingham.ac.uk/id/eprint/33199

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