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Title: Investigating the effect of emetic and aversive compounds on Dictyostelium identifies a novel non-sentient model for bitter tastant research
Author: Robery , Steven Jann
Awarding Body: Royal Holloway, University of London
Current Institution: Royal Holloway, University of London
Date of Award: 2013
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Nausea and vomiting are common but serious side effects associated with many therapeutic drugs. Whilst the physiological mechanisms behind the generation of the vomiting response are well characterised, the range of emetic stimuli that can generate the response are poorly understood. The potential of using Dictyostelium discoideum, a eukaryotic amoeba, as a model for predicting emetic liability was examined in this thesis. The effects of a range of known emetic and aversive compounds on Dictyostelium cell behaviour was investigated, resulting in the identification of a small number that strongly inhibited cell migration in a concentration-dependent and reversible manner. These active compounds included a range of bitter compounds and the pungent taslant, capsaicin. A Dictyostelium mutagenesis screen was then used to identify genes controlling sensitivity to bitter tastants. This screen identified a mutant containing a disrupted grlJ gene as showing partial resistance to phenylthiourea in growth and behavioural changes in movement. GrlJ is a Gprotein coupled receptor that regulates a phenylthiourea-dependent effect by inhibition of a phosphatidylinositol (PIP3) signalling pathway. A search for proteins sharing homology to GrlJ identified an uncharacterised GABAB-like receptor, QaNHA5, involved in the detection of phenylthiourea in Dictyostelium. This thesis has therefore identified Dictyostelium as a potentially useful model for the identification of bitter and pungent tastants. In addition, this thesis has identified the Dictyostelium protein, GrIJ, as well as an uncharacterised human protein, Q8NHA5, involved in the detection of the bitter tastant, phenylthiourea.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available