About the Project
The molecular mechanism of many chemicals and bioactive natural products remain unclear, despite wide use these chemicals as medicines or traditional remedies for the treatment diseases or as antibiotics, in food supplements, and in the agrochemical industry. Understanding the mechanisms of these chemicals provides numerous benefits including the development of novel medicines that are more potent or show reduced levels of side effects, or through helping our understanding of underlying cell signalling processes. Our research has developed the use of a simple eukaryotic model system, Dictyostelium discoideum, to improve our understanding of the molecular and cellular action of these wide-ranging compounds. Our recent studies have included the analysis of cannabinoids and medium chain fatty acids in epilepsy treatment and other disorders, Chinese traditional medicines in cancer treatment, flavonoids in the treatment of inherited diseases, identifying novel antibiotics, and developing ‘green’ herbicides. We now offer projects continuing in these areas, relating to compounds linked to health or medicinal effects, using Dictyostelium as the initial model system. Experiments will include the identification of molecular targets and related cell signalling pathways regulated by these compounds, the identification and characterisation of related compounds to provide new compounds (medicines or natural products) with improved function, and the translation of these discoveries to relevant pre-clinical or human models. The outcome of this project will be an improved understanding of the action and potency of bioactive compounds or natural products on Dictyostelium that may lead to the identification of potential molecular targets or improved medicines for disease treatments.
Applicants will be expected to have significant training/experience in molecular cell biology or related disciplines, with outstanding references.
2. Perry et al (2020) A new mechanism for Cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models. British Journal of Pharmacology, 1–17, doi.org/10.1111/bph.14892
3. Schaf, Damstra-Oddy & Williams (2019) Dictyostelium discoideum as a pharmacological model system to study the mechanisms of medicinal drugs and natural products. Int. J. Dev Biol. 63: 541 - 550
4. Sharma et al (2019) Gamma secretase orthologs are required for lysosomal activity and autophagic degradation in Dictyostelium discoideum, independent of PSEN (presenilin) proteolytic function, Autopahgy, 15(8):1407-1418
5. Kelly et al (2018) Diacylglycerol kinase (DGKA) regulates the effect of the epilepsy and bipolar disorder treatment valproic acid in Dictyostelium discoideum. Disease Models and Mechanisms. 11, dmm035600. Ranked in the top 5% of all research outputs for this journal in the first month
6. Warren, Walker & Williams (2018) All you need is fats – for seizure control: using amoeba to advance epilepsy research. Frontiers in Cellular Neuroscience. 12: 199
7. Cocorocchio et al (2018) Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues in Dictyostelium discoideum. Disease Models and Mechanisms. 29;11(1)
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