Transporter Biology Group - Honours projects available in 2010
An Honours project undertaken in this lab would be administered by the Discipline of Pharmacology.
- Molecular Basis for K+ coupling of Glutamate Transporters
Supervisor + contact details:
- Associate Professor Robert Vandenberg
- Associate Professor Renae Monique Ryan
Glutamate plays many vital roles in the central nervous system and it is important to tightly regulate glutamate concentrations to maintain dynamic signalling processes between neurones. Glutamate transport is coupled to the co-transport of 3 Na+, 1 H+ and the counter-transport of 1 K+, which is able to support a 106 fold gradient across the cell membrane. However, under ischaemic conditions following a stoke, the collapse of Na+ and K+ gradients reduces the concentrating capacity of the transporter and may lead to reverse transport and subsequent excitoxicity. In this project you will investigate the molecular basis for K+ counter-transport by glutamate transporters. The neutral amino acid transporter, ASCT, is closely related to the human glutamate transporters, but shows distinct differences. One such difference is that ASCT does not require K+ counter-transport. You will construct a series of chimeric transporters that are part glutamate transporter and part neutral amino acid transporter to identify domains of the transporter that are required for K+ coupling. The project will involve learning techniques in molecular biology, including PCR, DNA cloning, DNA sequencing and RNA transcription and also techniques in electrophysiology using Xenopus laevis oocytes.
- Characterization of Drug Binding sites on Glycine Transporters
Supervisor + contact details:
- Associate Professor Robert Vandenberg
- Associate Professor Renae Monique Ryan
Glycine is an unusual neurotransmitter in that it is both excitatory and inhibitory and a number of recent studies have suggested that inhibition of glycine transporter may be a very useful way of treating a variety of neurological disorders. Enhancement of excitatory neurotransmission by inhibition of the glycine transporter GLYT1 has recently been investigated as a potential antipsychotic therapy. Conversely, enhancement of inhibitory neurotransmission by inhibition of the glycine transporter GLYT2 shows particular promise in the development of novel analgesics in the treatment of chronic pain. This project will investigate the molecular basis for drug selectivity of GLYT1 and GLYT2 inhibitors so as to provide a detailed description of the three dimensional structure of the drug binding sites. This project will complement ongoing studies in the laboratory aimed at developing high affinity novel GLYT inhibitors as potential theraputics. In this project you will learn molecular biology techniques such as PCR, site-directed mutagenesis and also techniques in electrophysiology using Xenopus laevis oocytes.
Prospective honours students should come and see Robert Vandenberg or Renae Ryan to discuss these projects in more detail.
