Bosch CJ Martin Fellow
Dr Renae Ryan is a CJ Martin Fellow in the Bosch Institute. Dr Ryan completed her PhD in the Discipline of Pharmacology under the supervision of Associate Professor Rob Vandenberg, Head of the Molecular Pharmacology Laboratory within the Bosch Institute.
Dr Ryan has recently returned to the Bosch Institute following a three year Postdoctoral Fellowship, one year in the lab of Eric Gouaux at Columbia University and two years at the NIH/NINDS with Joe Mindell.
Dr Ryan’s research focuses on the structure and function of glutamate transporters. These transporters play an important role in regulating normal neurotransmission in the brain and their dysfunction has been implicated in disease states such as Alzheimer's disease, Motor Neurone Disease, and ischemia following a stroke. Dr. Ryan was involved in determining the crystal structure of a bacterial glutamate transporter which has revealed an atomic level snapshot of this protein. The structure of the bacterial transporter allows us to predict the structure of the human glutamate transporters, the conformational changes that occur during transport and also how drugs bind to and affect these proteins. Her work in this area has been highly successful and has been acknowledged with two articles published in Nature1 and Nature Structural and Molecular Biology2 earlier this year.
(a) Location of sodium-binding sites on the permeation pathway of aspartate. Two protomers of GltPh are shown. N-terminal cylinders are in ribbon representation, the TM helices in the C-terminal protein cores are shown as cylinders and bound aspartate is shown in stick representation. HP2 (red) serves as an extracellular gate and opens to afford aspartate access to the binding site. Sodium 2 (purple) serves as a lock on the gate, providing additional energy necessary for its closure. Below the substrate-binding site is sodium 1 (green) and bound solvent (red sphere). The proposed intracellular gate is formed by HP1 (yellow), TM7 (orange) and TM8 (magenta), which are held together by sodium 1. The proposed permeation pathway for the substrate is shown as a grey line and motions of HP2 are shown as a dashed double-headed arrow.
(b) View of the aspartate-binding site showing HP1 (yellow), TM7 (orange), HP2 (red) and TM8 (magenta). A remarkable number of polar contacts solvate the highly charged substrate.
Dr Ryan’s CJ Martin Fellowship will continue for a final 2 years and she is looking forward to resuming her research in Associate Professor Vandenberg’s Lab. Renae will ultimately seek her own funding and hopes to have her own lab that will focus on the structure and function of membrane proteins by the time the new ARC building is completed.
References
- Boudker O*, Ryan RM*, Yernool D, Shimamoto, K and Gouaux E (2007) Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter. Nature 445, 387-393. (*equal authorship)
- Ryan RM and Mindell JA (2007) The uncoupled chloride conductance of a bacterial glutamate transporter homolog. Nature Structural and Molecular Biology, 14, 365-71.
