Project description
Two related compounds (xanthurenic acid and caelestine C) have been shown to be modulators of glutamatergic neurotransmitter activity in synapses. Xanthurenic acid (XA) is a tryptophan metabolite natively present in the CNS at micromolar concentrations and demonstrated to promote activation of metabotropic glutamate receptors (subtypes mGluR 2, 3), and to inhibit vesicular glutamate transport. Caelestine C is a brominated quinoline carboxylic acid from the Australian ascidian Aplidium caelestis. Chemical analogs of caelestines with minor differences in benzene ring substituents have been found to differentially antagonize NMDA (N-methyl-D-aspartate) and non-NMDA glutamate receptors. A general concern with ion channels and receptors as candidate GBM targets is that these signaling pathways also are normal mechanisms of function in neurons and glia. We propose that using combinations of agents at threshold doses could enable focusing of the pharmacological effects on brain cancer cells, taking advantage of GBM subtype ‘fingerprints’ (i.e., the class-specific patterns of upregulated ion and water channels in the cancer cells), a step towards the goal of minimizing off-target effects. In this project, you will evaluate these two compounds in combination with novel anti-invasive compounds characterised in our research group.
Assumed knowledge
Biochemistry, basic cell biology
Supervisors research focus
My research is focused on investigating the role of transport proteins in disease and pathology (humans) and mitigating abiotic stress in crop plants. Research projects have potential biotechnology outcomes.
Note: You need to register interest in projects from different supervisors (not a number of projects with the one supervisor).
You must also contact each supervisor directly to discuss both the project details and your suitability to undertake the project.